Classifications

• • 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
  • G01N15/1456—Optical investigation techniques, e.g. flow cytometry without spatial resolution of the texture or inner structure of the particle, e.g. processing of pulse signals
  • G01N15/1459—Optical investigation techniques, e.g. flow cytometry without spatial resolution of the texture or inner structure of the particle, e.g. processing of pulse signals the analysis being performed on a sample stream
• • 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
  • G01N2015/0038—Investigating nanoparticles
• • 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
  • G01N15/02—Investigating particle size or size distribution
  • G01N15/0205—Investigating particle size or size distribution by optical means
  • G01N2015/025—Methods for single or grouped particles
• • 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
  • G01N2015/1402—Data analysis by thresholding or gating operations performed on the acquired signals or stored data

Definitions

• a large portion of the micro-contamination industry is reliant on the use of particle counters, such as are described in a large number of U.S. Patents, including U.S. Patent Nos. 3,851 ,169, 4,348,111 , 4,957,363, 5,085,500, 5,121 ,988, 5,467,188, 5,642,193, 5,864,399, 5,920,388, 5,946,092, and 7,053,783.
• U.S. Patent Nos. 4,728,190, 6,859,277, and 7,030,980, 5,282,151 also disclose particle counters and are hereby incorporated by reference in their entirety. Aerosol particle counters are often used to measure air-born particle contamination in clean-rooms and clean zones. Liquid phase particle counters are often used to measure particulate contamination in the water treatment and chemical processing industries.
• Particle counters capable of spatially resolving electromagnetic radiation scattered or emitted by particles typically employ two-dimensional detectors, such as the particle detector described in U.S. Patent No. 5,282,151.
• U.S. Patent No. 7,170,601 and U.S. Patent Application Publication No. US 2006/0001874 A1 also disclose a particle counter capable of spatially resolving electromagnetic radiation scattered or emitted by particles. These optical particle counters collect scattered or emitted electromagnetic radiation in a direction parallel to the fluid flow direction and are capable of spatially resolving the source of scattered or emitted electromagnetic radiation along directions perpendicular to the fluid flow direction.
• particle counters lack the ability to spatially resolve scattered or emitted electromagnetic radiation in a direction parallel to the fluid flow direction.
• the particle detection systems described herein utilize a geometrical configuration which allows for spatially resolving electromagnetic radiation scattered or emitted by particles in directions parallel to the fluid flow direction as well as perpendicular to the fluid flow direction.
• a particle detection system capable of spatially resolving the interaction of particles with a beam of electromagnetic radiation. Using a specific electromagnetic beam cross sectional shape and orientation, the detection sensitivity of a particle detection system can be improved. Also described herein are methods for detecting and sizing particles in a manner that has low background signal and allows for spatially resolving the scattering or emission of electromagnetic radiation from particles.
• a particle detection system comprises a flow cell for containing a fluid flowing through the flow cell in a flow direction; a source for generating a beam of electromagnetic radiation having a cross sectional profile having a major axis and a minor axis, the source positioned to direct the beam through the flow cell, wherein the angle between the major axis of the cross sectional profile of the beam and the flow direction is non-orthogonal, and wherein particles contained within the fluid interact with the beam thereby generating scattered or emitted electromagnetic radiation; and a two-dimensional detector positioned in optical communication with the flow cell for receiving at least a portion of the scattered or emitted electromagnetic radiation.
• a method of this aspect comprises the steps of: providing particles in a fluid having a flow direction; passing a beam of electromagnetic radiation having a cross sectional profile having a major axis and a minor axis through the fluid, wherein the angle between the major axis and the flow direction is non-orthogonal and wherein particles interact with the beam thereby generating scattered or emitted electromagnetic radiation; and detecting at least a portion of the scattered or emitted electromagnetic radiation with a two- dimensional detector, thereby detecting the particles.
• the scattered or emitted electromagnetic radiation is collected or directed onto the two-dimensional detector by a system of optics.
• the angle between the beam cross sectional major axis and the flow direction is non-parallel.
• any optical element may be useful with the methods and systems described herein including, but not limited to: a lens, a mirror, a filter, a beam splitter, an optical fiber, an optical waveguide, a window, an aperture, a slit, a prism, a grating, a polarizer, a wave plate, a crystal, and any combination of these or other optical elements.
• the scattered or emitted electromagnetic radiation is imaged onto the two-dimensional detector by the system of optics.
• a particle counter optionally includes auto-focusing of the system of optics to properly image scattered or emitted radiation from a particle onto a two-dimensional detector.
• useful two-dimensional detectors comprise an array of detector elements positioned such that a plurality of detector elements receive the scattered or emitted electromagnetic radiation.
• Any two-dimensional detector can be useful with the systems and methods for detecting or sizing particles including, but not limited to: a two-dimensional array of photodetectors, a charge-coupled device (CCD) detector, a complementary metal- oxide-semiconductor (CMOS) detector, a metal-oxide-semiconductor (MOS) detector, an active pixel sensor, a microchannel plate detector, a two-dimensional array of photomultiplier tubes, a two-dimensional array of photodiodes, a two- dimensional array of phototransistors, a two-dimensional array of photoresistors, and a photoconductive film.
• CCD charge-coupled device
• CMOS complementary metal- oxide-semiconductor
• MOS metal-oxide-semiconductor
• the two-dimensional detector has an orientation positioned to allow for a sharply focused image of the scattered or emitted electromagnetic radiation across an active area of the two- dimensional detector.
• the two- dimensional detector has an orientation positioned for providing a spatially resolved image of the scattered or emitted electromagnetic radiation, wherein the scattered or emitted electromagnetic radiation is spatially resolved in a first direction parallel to a propagation axis of the beam and in a second direction parallel to the flow direction.
• the orientation of the two-dimensional detector provides for a spatially resolved image of the scattered or emitted electromagnetic radiation in a first direction parallel to a propagation axis of the beam and in a second direction parallel to the major axis of the beam cross sectional profile.
• a method of this aspect comprises the steps of: providing particles suspended within a fluid flowing in a flow direction; passing a beam of electromagnetic radiation through the fluid, wherein the beam has a cross sectional profile having a major axis and a minor axis and wherein the angle between the major axis and the flow direction is non-orthogonal and wherein the particles interact with the beam thereby generating scattered or emitted electromagnetic radiation; and directing at least a portion of the scattered or emitted electromagnetic radiation onto a two-dimensional detector, thereby spatially resolving the scattered or emitted electromagnetic radiation in a first direction parallel to a propagation axis of the beam and in a second direction parallel to the major axis of the beam cross sectional profile.
• the scattered or emitted electromagnetic radiation when the scattered or emitted electromagnetic radiation reaches the two-dimensional detector, it is detected by the two-dimensional detector, thereby generating a plurality of output signals corresponding to intensities of the scattered or emitted electromagnetic radiation.
• the angle between the beam cross sectional major axis and the flow direction is non-parallel.
• the electromagnetic radiation scattered or emitted by the particles is spatially resolved from electromagnetic radiation scattered or emitted by walls of a flow cell surrounding the fluid.
• electromagnetic radiation scattered or emitted by a first particle interacting with the beam is imaged onto a first position of the two- dimensional detector and scattered or emitted electromagnetic radiation generated by a second particle, having a different position than the first particle, is imaged onto a second position of the two-dimensional detector.
• the method further comprises analyzing a signal provided by the detector in response to the scattered or emitted electromagnetic radiation.
• the analysis comprises one or more techniques including time delay integration (TDI), image threshold analysis, image shape analysis, pulse height analysis, pulse width analysis, or other techniques useful for detecting particles.
• a method of this aspect comprises the steps of: providing a particle suspended within a fluid flowing in a flow direction through a flow cell; passing a beam of electromagnetic radiation through the fluid, wherein the beam has a cross sectional profile having a major axis and a minor axis and wherein the angle between the major axis and the flow direction is non-orthogonal and wherein the particle interacts with the beam thereby generating scattered or emitted electromagnetic radiation; imaging at least a portion of the scattered or emitted electromagnetic radiation onto a two-dimensional detector; determining the intensity of the scattered or emitted electromagnetic radiation on the two-dimensional detector; and comparing the intensity of the scattered or emitted electromagnetic radiation with one or more threshold reference values, thereby determining the size of the particle.
• the threshold reference values may correspond to intensities of scattered or emitted electromagnetic radiation from particles of known sizes; if the intensity of electromagnetic radiation scattered or emitted from a particle falls between two threshold reference values, the particle is sized between the known particle sizes corresponding to those threshold reference values.
• the threshold reference values are dependent upon the position of the particle within the flow cell. In another embodiment, the threshold reference values are dependent upon the flow rate of the fluid. In yet another embodiment, the flow rate of the fluid may be dependent upon the position within the flow cell; for example, fluid flowing near the walls of the flow cell may be flowing slower than fluid flowing near the center of the flow cell. In another embodiment, the threshold reference values are dependent upon the intensity of the beam. In a further embodiment, the threshold reference values are dependent upon both the intensity of the beam and the position within the flow cell.
• the method may further comprise the step of determining the position of the particle within the flow cell. In some embodiments, this step is preferred to occur before the step of comparing the intensity of the scattered or emitted electromagnetic radiation with one or more threshold reference values. In another embodiment, the position of the particle within the flow cell is used to determine one or more threshold reference values for subsequent comparison.
• Figure 1 provides a schematic diagram of an embodiment of a particle detection system.
• Figure 2A provides a perspective view of an embodiment of a particle detection system.
• Figure 2B provides a perspective view of an embodiment of a particle detection system.
• Figure 3A shows an alternative perspective of a beam of electromagnetic radiation illuminating a flow cell in a particle detection system.
• Figure 3B shows an expanded view of a region of Figure 3A.
• Figure 3C shows an overhead view of the flow cell of Figure 3A.
• Figure 3D shows a view of the flow cell of Figure 3A along the fluid flow direction.
• Figure 3E shows a side view of the flow cell of Figure 3A.
• Figure 4A shows an image detected by a two-dimensional detector of a particle detection system, where the angle between the beam cross sectional profile major axis and the flow direction is 90°.
• Figure 4B shows an image detected by a two-dimensional detector of a particle detection system, where the angle between the beam cross sectional profile major axis and the flow direction is 45°.
• Figure 4C shows an image detected by a two-dimensional detector of a particle detection system, where the angle between the beam cross sectional profile major axis and the flow direction is 21 °.
• Figure 5 shows data illustrating the counting efficiency of 80 nm particles by a particle detection system at various angles between the beam cross sectional profile major axis and the flow direction.
• Figure 6 shows data illustrating the counting efficiency of 125 nm particles by a particle detection system at various angles between the beam cross sectional profile major axis and the flow direction.
• Figure 7 shows data summarizing the counting efficiency of 80 and 125 nm particles at various angles between the beam cross sectional profile major axis and the flow direction.
• Figure 8 shows views of an exemplary capillary mount.
• Figure 9 illustrates an exemplary autofocus system.
• Flow direction refers to an axis parallel to the direction the bulk of a fluid is moving when a fluid is flowing.
• the flow direction is parallel to the path the bulk of the fluid takes.
• the flow direction may be considered tangential to the path the bulk of the fluid takes.
• Beam propagation axis refers to an axis parallel to the direction of travel of a beam of electromagnetic radiation.
• Cross sectional profile refers to a profile formed by a plane cutting through an object at a right angle to an axis of propagation or travel.
• the cross sectional profile of a beam of electromagnetic radiation is a profile of the beam formed by a plane perpendicular to the beam propagation axis.
• the cross sectional profile of a flow cell is a profile of the flow cell formed by a plane perpendicular to the flow direction.
• Major axis refers to an axis parallel to the longest axis of a shape.
• the major axis of an ellipse is parallel to the longest diameter of the ellipse
• the major axis of a rectangle is parallel to the long dimension of a rectangle.
• Minor axis refers to an axis parallel to the shortest axis of a shape.
• the minor axis of an ellipse is parallel to the shortest diameter of the ellipse
• the minor axis of a rectangle is parallel to the short dimension of a rectangle.
• Optical communication refers to an orientation of components such that the components are arranged in a manner that allows light or electromagnetic radiation to transfer between the components.
• Optical axis refers to a direction along which electromagnetic radiation propagates through a system.
• spot size refers to the size that an image of a point or object is focused to by one or more lenses.
• the spot size refers to the root mean square (RMS) spot size.
• the RMS spot size is the size of a spot which includes 66% of the total energy, for example 66% of the total energy of a focused beam of electromagnetic radiation.
• Tro-dimensional detector refers to a detector capable of spatially resolving input signals (e.g., electromagnetic radiation) in two dimensions across an active area of the detector.
• a two-dimensional detector is capable of generating an image, for example an image corresponding to an intensity pattern on the active area of the detector.
• a preferred two-dimensional detector comprises an array of detector elements or pixels, for example: a two-dimensional array of photodetectors, a charge-coupled device (CCD) detector, a complementary metal-oxide-semiconductor (CMOS) detector, a metal-oxide-semiconductor (MOS) detector, an active pixel sensor, a microchannel plate detector, a two-dimensional array of photomultiplier tubes, a two-dimensional array of photodiodes, a two-dimensional array of phototransistors, a two-dimensional array of photoresistors, or a photoconductive film.
• CCD charge-coupled device
• CMOS complementary metal-oxide-semiconductor
• MOS metal-oxide-semiconductor
• an active pixel sensor for example: a two-dimensional array of photodetectors, a charge-coupled device (CCD) detector, a complementary metal-oxide-semiconductor (CMOS) detector, a metal-oxid
• Particle refers to a small object which is often regarded as a contaminant.
• a particle can be any material created by the act of friction, for example when two surfaces come into mechanical contact and there is mechanical movement.
• Particles can be composed of aggregates of material, such as dust, dirt, smoke, ash, water, soot, metal, minerals, or any combination of these or other materials or contaminants.
• Particles may also refer to biological particles, for example, viruses, spores and microorganisms including bacteria, fungi, archaea, protists, other single cell microorganisms and specifically those microorganisms having a size on the order of 1 -15 ⁇ m.
• a particle may refer to any small object which absorbs or scatters light and is thus detectable by an optical particle counter.
• particle is intended to be exclusive of the individual atoms or molecules of a carrier fluid, for example water molecules, oxygen molecules, helium atoms, nitrogen molecules, etc.
• Some embodiments of the present invention are capable of detecting, sizing, and/or counting particles comprising aggregates of material having a size greater than 50 nm, 100 nm, 1 ⁇ m or greater, or 10 ⁇ m or greater.
• Specific particles include particles having a size selected from 50 nm to 50 ⁇ m, a size selected from 100 nm to 10 ⁇ m, or a size selected from 500 nm to 5 ⁇ m.
• a particle detection system of some embodiments comprises a flow cell for containing a fluid flowing through the flow cell in a flow direction.
• the flow cell comprises a transparent-walled sample cell.
• Useful flow cells comprise flow cells capable of transporting fluids comprising liquids or gases.
• the flow direction of the fluid also provides a reference axis useful for defining additional components of the systems and methods described herein.
• the flow cell has a cross sectional profile having a first longer side and a second shorter side.
• the first longer side has a length selected from the range of 0.25 mm to 10 mm, preferably 5 mm.
• the second shorter side has a width selected from the range of 80 ⁇ m to 500 ⁇ m, preferably 100 ⁇ m.
• the flow cell cross section has an aspect ratio, equal to the length of the longer side divided by the width of the shorter side, greater than or equal to 20, or greater than or equal to 50.
• the first longer side of the flow cell is aligned parallel to an electromagnetic beam propagation axis and the second shorter side of the flow cell is aligned perpendicular to an electromagnetic beam propagation axis.
• a particle detection system of some embodiments also comprises a source for generating a beam of electromagnetic radiation.
• the beam of electromagnetic radiation has a cross sectional profile having a major axis and a minor axis.
• Such a cross sectional profile may be generated by the source itself or by the source in combination with one or more beam shaping elements including lenses, mirrors, apertures, or other beam shaping elements.
• the beam cross sectional profile has an elliptical or rectangular shape. In other embodiments, the beam cross sectional profile has a shape that is substantially elliptical or substantially rectangular.
• the beam cross sectional profile has a width along the minor axis selected from between 5 ⁇ m and 100 ⁇ m, preferably 40 ⁇ m. In another embodiment preferred for some applications, the beam cross sectional profile has a width along the major axis selected from between 50 ⁇ m and 1200 ⁇ m, preferably 600 ⁇ m. In an exemplary embodiment, the beam cross sectional profile has a width along the major axis which extends to or beyond the walls of the flow cell. In this and other embodiments, the particle detection system is capable of providing a volumetric analysis of the fluid. In another embodiment, the beam cross sectional profile has a width along the major axis which does not reach the walls of the flow cell. In this and other embodiments, the particle detection system is capable of providing a non- volumetric analysis of the fluid.
• the source is positioned to direct the beam through a flow cell such that the angle between the major axis of the beam cross sectional profile and the flow direction is non-orthogonal.
• the angle between the major axis of the beam cross sectional profile and the flow direction is selected from the range of 5° to 85°, or preferably from the range of 16° to 26°, or more preferably from the range of 20° to 22°.
• the beam cross profile major axis may be orthogonal or parallel to the flow direction.
• the particle detection systems in another embodiment further comprise a two dimensional detector positioned in optical communication with the flow cell.
• a detector positioned in optical communication with the flow cell is useful for detecting at least a portion of electromagnetic radiation that is scattered or emitted by particles interacting with the beam.
• the two-dimensional detector comprises an array of detector elements positioned such that a plurality of detector elements receives at least a portion of the scattered or emitted electromagnetic radiation.
• Useful two-dimensional detectors include, but are not limited to: a two-dimensional array of photodetectors, a CCD detector, a CMOS detector, a MOS detector, an active pixel sensor, a microchannel plate detector, a two-dimensional array of photomultiplier tubes, a two-dimensional array of photodiodes, a two-dimensional array of phototransistors, a two-dimensional array of photoresistors, and a photoconductive film.
• Some embodiments of this aspect may further comprise a system of optics.
• Optical elements of such a system are useful for shaping the beam of electromagnetic radiation, or for collecting or directing electromagnetic radiation scattered or emitted by particles interacting with the beam onto the two-dimensional detector.
• a system of optics may comprise one or more optical elements.
• a system of optics may comprise two aspherical lenses.
• Useful optical elements include: a lens, a mirror, a filter, a beam splitter, an optical fiber, an optical waveguide, a window, an aperture, a slit, a prism, a grating, a polarizer, a wave plate, a crystal, and any combination of these or other shaping, focusing, or directing elements.
• the system of optics images the scattered or emitted radiation onto the two-dimensional detector.
• the scattered or emitted electromagnetic radiation is focused to a spot on the two-dimensional detector having a size selected from the range of 5 ⁇ m to 80 ⁇ m, preferably 12 ⁇ m.
• a system of optics for collecting or directing the scattered or emitted electromagnetic radiation is preferably positioned between the flow cell and the two- dimensional detector.
• the two-dimensional detector is oriented non-orthogonal to the optical axis of the system of optics for collecting or directing the beam onto the two dimensional detector.
• Non-orthogonal in this embodiment is in reference to the position of the plane of the two-dimensional detector which contains the active elements in relation to the optical axis of the system of optics.
• the optical axis of the system of optics is oriented non-orthogonal to the major axis of the beam cross sectional profile.
• the two-dimensional detector has an orientation positioned to allow for a sharply focused image of the scattered or emitted electromagnetic radiation across an active area of the two-dimensional detector.
• the two dimensional detector has an orientation positioned for providing a spatially resolved image of the scattered or emitted electromagnetic radiation, wherein the scattered or emitted electromagnetic radiation is spatially resolved along a first axis parallel to the beam propagation axis and along a second axis parallel to the major axis of the beam cross sectional profile.
• Figure 1 shows a schematic diagram of an embodiment of a particle detection system.
• source 100 generates a beam of electromagnetic radiation 110 directed through flow cell 120 parallel to beam propagation axis 115.
• beam 110 is shaped and directed by a lens 130 before entering flow cell 120.
• Particles suspended in the fluid flowing through flow cell 120 generate scattered or emitted electromagnetic radiation 160 when they interact with beam 110.
• An optical system 170 collects and focuses the scattered or emitted electromagnetic radiation 160 along optical detection axis 175 and onto a two-dimensional detector 180.
• optical system 170 is comprised of two asphehc lenses.
• FIG. 2A shows a perspective view of a particle detection system embodiment.
• source 200 generates a beam of electromagnetic radiation 210 which is directed through flow cell 220.
• Beam 210 is shaped and directed by a lens 230 before entering flow cell 220.
• beam 210 is shaped by lens 230 to have a cross sectional profile 235 having an elliptical shape having a major axis parallel to axis 205 and a propagation axis orthogonal to flow direction 250.
• Particles 240 flow through flow cell 220 parallel to flow direction 250.
• Cross sectional profile major axis 205 forms an angle 290 with flow direction 250.
• Particles flow through the region of the flow cell 220 that is illuminated by beam 210 and interact with the beam, generating scattered or emitted electromagnetic radiation 260.
• Scattered or emitted electromagnetic radiation 260 is collected and directed by optical system 270 onto two-dimensional detector 280 along optical detection axis 275.
• two-dimensional detector 280 is non-orthogonal to optical detection axis 275.
• FIG. 2B shows a perspective view of an alternative particle detection system embodiment.
• source 200 generates a beam of electromagnetic radiation 210 which is directed through flow cell 220.
• Beam 210 is shaped and directed by a lens 230 before entering flow cell 220.
• beam 210 is shaped by lens 230 to have a cross sectional profile 235 having an elliptical shape having a major axis parallel to axis 205 and a propagation axis non-orthogonal to flow direction 250.
• Particles 240 flow through flow cell 220 parallel to flow direction 250.
• flow direction 250 and cross sectional profile major axis 205 are orthogonal.
• Particles flow through the region of the flow cell 220 that is illuminated by beam 210 and interact with the beam, generating scattered or emitted electromagnetic radiation 260.
• Scattered or emitted electromagnetic radiation 260 is collected and directed by optical system 270 onto two-dimensional detector 280 along optical detection axis 275.
• two-dimensional detector 280 is non-orthogonal to optical detection axis 275.
• Figure 3A shows an alternative perspective view of the beam of electromagnetic radiation illuminating the flow cell.
• beam 310 is traveling parallel to beam propagation axis 315.
• Particles and fluid flowing in flow cell 320 travel parallel to flow direction 350.
• Figure 3B shows an expanded view of a region of flow cell 320.
• Particles 340 travel parallel to flow direction 350 along trajectories 355 and interact with beam 310 in regions 365 where they generate scattered or emitted electromagnetic radiation.
• Figures 3C, 3D, and 3E show various views of the flow cell 320 and beam 310.
• Figure 3C shows a view of the flow cell 320 and beam looking along the propagation axis of the beam. The cross sectional profile 335 of the beam is shown in this view.
• cross sectional profile 335 has an elliptical shape.
• Figure 3C also shows a set of axes for this view showing flow direction 350, an optical collection axis 375 and beam cross sectional profile major axis 305.
• Angle 390 is formed between flow direction 350 and beam cross sectional profile major axis 305. In various embodiments, angle 390 is different from 90°; that is, flow direction 350 and beam cross sectional profile major axis 305 are non-orthogonal. In some embodiments, however, angle 390 is 90°.
• Figure 3D shows a view of flow cell 320 looking along flow direction. Beam 310 propagates along beam propagation axis 315 illuminating flow cell 320.
• FIG. 3E shows a view along the optical collection axis. Particles and fluid flow in flow direction 350 through flow cell 320. Beam 310 propagates along beam propagation axis 315 illuminating flow cell 320. In this embodiment, only a small portion of flow cell 320 is illuminated by beam 310. The illuminated region is indicated by the dashed lines in Figure 3E. However, all of the fluid flows through the beam.
• Figures 4A, 4B, and 4C show images detected by a two-dimensional detector of a particle detection system embodiment for various angles between the flow direction and beam cross sectional profile major axis. These grey-scale images represent intensities observed by a two-dimensional detector where black is low intensity and white is high intensity. These images represent a view of the flow cell similar to that of Figure 3E. In these images, the bright white spot at the top of the image represents scattered or emitted electromagnetic radiation generated by the beam interacting with the walls of the flow cell where the beam enters the flow cell. The bright white spot at the bottom of the image represents scattered or emitted electromagnetic radiation generated by the beam interacting with the walls of the flow cell where the beam exits the flow cell.
• beam cross sectional profile major axis 305 is perpendicular to flow direction 350; i.e., angle 390 is 90°.
• the bright white spot in the center of the image is a result of contamination on the walls of the flow cell.
• the faint line travelling from the top of the image to the bottom of the image represents electromagnetic radiation scattered by fluid in the flow cell interacting with beam which propagates along axis 315.
• a faint spot brighter than its surroundings may indicate detection of a single particle (indicated by an arrow in the image).
• the bright white spot is likely the result of contamination located on the walls of the flow cell interacting with the beam.
• beam cross sectional profile major axis 305 and flow direction 350 form an angle 390 of approximately 45°.
• the two bright white spots along the left side of the image are a result of contamination on the walls of the flow cell.
• the cross-sectional profile of the beam is now at an angle 390 of 45°, the scattered or emitted electromagnetic radiation from the contamination no longer obscures major portions of the flow region, but appears at the sides of the image.
• the faint glow travelling from the top of the image to the bottom of the image represents electromagnetic radiation scattered by fluid in the flow cell interacting with beam propagating along axis 315.
• several faint spots brighter than the surroundings may indicate detection of particles (3 examples indicated by arrows in the image).
• the bright contamination spot on the left side of the image appears to be from contamination on one side of the flow cell, as indicated by element 395 in the inset, while the particle indicated by the long arrow appears to be from a particle travelling near the opposite side of the flow cell, as indicated by element 340 in the inset.
• beam cross sectional profile major axis 305 is aligned to flow direction 350 at an angle 390 of approximately 21 °.
• the faint glow travelling from the top of the image to the bottom of the image represents electromagnetic radiation scattered by fluid in the flow cell interacting with beam propagating along axis 315.
• several faint spots brighter than the surroundings indicate detection of particles (5 examples indicated by arrows in the image).
• the particles have a longer distance to travel through the beam, resulting in more light scattered and smaller particles able to be detected.
• Polystyrene latex particles having sizes of 80 nm and 125 nm were allowed to flow through a particle detection system in order to determine the counting efficiency of the particles.
• the angle between the flow direction and the beam cross sectional profile major axis was varied at 3 directions: a 21 ° angle between the flow direction and the beam cross sectional profile major axis; a 45° angle between the flow direction and the beam cross sectional profile major axis; and a 90° angle between the flow direction and the beam cross sectional profile major axis.
• Figure 5 shows data illustrating the counting efficiency of 80 nm particles as a function of the angle between the flow direction and beam cross sectional profile major axis.
• the counting efficiency of the 80 nm particles drops as the angle is increased from 21 ° to 45° to 90°.
• Figure 6 shows similar data illustrating the counting efficiency of 125 nm particles. As seen in Figure 6, the counting efficiency of 125 nm particles is near 100% at 21 ° and 45°, but has a significant drop off to less than 80% counting efficiency at an angle of 90°.
• Figure 7 summarizes the counting efficiency of 80 nm and 125 nm polystyrene latex particles.
• a particle counter or particle detection system comprises such a capillary mount.
• Imaging-based particle counters of the present invention optionally include capillary mounts for particle counting with integral seals, for example, using a rigid polymer (e.g., Kel-f at 80 Shore D) that is formed either by machining or molding to create a series of concentric seals around a capillary aperture integral to the holder.
• a rigid polymer e.g., Kel-f at 80 Shore D
• Use of a capillary mount with an integral seal is beneficial for some applications as it cuts the number of potential leak paths, eliminates components that can be incorrectly installed and reduces the number of tolerances to ensure a more uniform seal pressure.
• FIG. 8 illustrates a perspective view of an exemplary capillary mount 800.
• Capillary mount 800 includes a plurality of sealing regions 801 for creating a seal with capillary.
• Capillary mount 800 also includes a flow cell and a plurality of window regions 802 for permitting the entry and exit of a laser beam into the flow cell. Additional window regions 803 are included for transmitting scattered light to a detector.
• capillary mount 800 is a unitary structure; that is it comprises a single piece of material for forming a seal with one or more capillaries.
• the laser path in a particle detector is tipped relative to a capillary cell.
• the beam cross sectional profile major axis is oriented non- orthogonal to the flow direction within the capillary cell.
• the beam propagation axis is oriented non-orthogonal to the flow direction within the capillary cell. For example, these axes can be oriented at a relative angle of 69° or 21 °.
• the detector and capillary are tipped relative to any sensor imaging optics, for example a system of optics as described above.
• Imaging- based particle counters of the present invention optionally include auto-focusing using either particle spot sizes or laser beam structure or a combination of both.
• the location of the detector along the optical axis of the imaging optics can be adjusted by translation to achieve the best focus of the scattered or emitted radiation, but must also keep the image in the same location on the detector throughout the range of translation.
• a method for achieving this comprises mounting the detector at a fixed angle to the optical axis of the imaging optics and translating the detector along the imaging axis to focus.
• the detector is mounted on a linear rail system aligned to the optical axis for translating the detector along the optical axis.
• a spring is mounted to preload the imaging optics against one side of an angled plane to increase the precision of a translation stepper motor (e.g., by a factor of 5 or greater), to allow for a smaller increment of linear motion ⁇ e.g., 2 ⁇ m or less) per stepper motor step.
• a particle counter or particle detection system comprises an autofocus system.
• Figure 9 illustrates a specific autofocusing system embodiment 900.
• a capillary cell is mounted in capillary mount 901 and detector 902 is mounted at an angle relative to imaging optics housed within block 903.
• a linear rail system 904 is attached to detector 902 and stepper motor 905 for translation of detector 902 along the optical axis of the imaging optics housed within block 903.
• electromagnetic radiation is scattered from or emitted by a particle interacting with a beam of electromagnetic radiation of a particle detection system; scattered or emitted electromagnetic radiation which reaches the two- dimensional detector is detected, thereby generating a plurality of output signals corresponding to intensities of the scattered or emitted electromagnetic radiation. These output signals can be further processed and/or analyzed to determine a characteristic of the particle.
• output signals from every element of the two- dimensional detector are recorded or transmitted to a processor for further analysis.
• output signals from a sub-array i.e., only a portion of the elements of the two dimensional detector are recorded or transmitted to a processor for further analysis.
• only a portion of the output signals of the sub-array are utilized in determining a characteristic of a particle. Such a region of interest is useful, for example, for producing better size resolution of detected particles and/or preventing growth of the sample volume undergoing detection.
• the entire two-dimensional detector may image the entire flow cell of a particle detection system.
• a specific sub-array may correspond to output signals of an imaged region of a flow cell, for example the region of the flow cell illuminated by a beam of electromagnetic radiation.
• a sub- array may correspond to output signals of an imaged region of a flow cell illuminated by a beam of electromagnetic radiation but excluding the walls of the flow cell.
• a region of interest for example, may comprise output signals corresponding to the imaged region of a flow cell illuminated by the center of the beam of electromagnetic radiation and/or where the intensity of the beam of electromagnetic radiation is substantially uniform.

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