Fluid refractive index optimization particle counter

Abstract

To provide an optical particle counter system capable of analyzing particles in consideration of a refractive index of a carrier fluid to be analyzed.SOLUTION: An optical particle counter 100 includes a light source 220 for generating an electromagnetic radiation beam, a floating chamber 210 that flows a fluid containing particles along a flowing direction through the electromagnetic radiation beam, a light collection system 230 that collects electromagnetic radiation scattered or emitted from the particles to direct the radiation toward a detector 240, and a refraction index optimizer 101 connected to one or more of the light source, the light collection system and the detector so as to be operative to include optical communications.SELECTED DRAWING: Figure 1

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001]

[0001] This application claims the benefit of priority to U.S. Provisional Patent Application No. 62 / 725,777, filed August 31, 2018, the entirety of which is incorporated by reference herein to the extent not inconsistent herewith.

[0002] 2. Background of the Invention

[0003]

[0002] Particle counters play an important role in modern manufacturing technology because they monitor the environment for micro- and nano-scale particles that are problematic in a variety of industries, including semiconductor manufacturing and pharmaceutical or biotechnology production. As manufacturing processes advance, the need for detection, characterization, or removal of smaller and smaller particles becomes necessary.

[0004]

[0003] One common type of particle counter is the optical particle counter. These counters monitor a fluid flow and characterize the particles therein by projecting electromagnetic radiation (typically via a laser) into a flow cell. The electromagnetic radiation interacts (scatters, reflects, obscures, emits, etc.) with particles found within the flow cell. The electromagnetic radiation is then analyzed to determine the number or characteristics of particles present in the flow cell.

[0005]

[0004] As particle size decreases, the complexity of the optics for detecting particles increases dramatically. For detection of particles below 50 nm (which increases as particle size decreases), very powerful lasers and detectors must be precisely aligned to accurately detect and characterize the particles, and often require extensive calibration to be effective and accurate. However, many industries use a variety of different fluids in clean rooms or controlled environments, and changes in the refractive index of the fluid being analyzed can reduce or eliminate the effectiveness of the particle detector, since changes in the refractive index change the path of the electromagnetic radiation as it passes through the flow cell. The change in the path can change the ideal measurement point (focus) for the collection and / or detection system that analyzes the electromagnetic radiation, and may not provide an accurate characterization of the particles passing through the flow cell. In some cases, particle counters may be manually recalibrated, but calibration is required every time a fluid with a different refractive index is analyzed with the particle counter. Calibration is time consuming, expensive, and requires the particle counter to be taken offline.

[0006]

[0005] As can be seen from the above, there remains a need in the art for an optical particle counting system that can be used with different liquid carrier fluids without the need for recalibration, which is accomplished by taking into account the refractive index of the carrier fluid. Further, there is a need for an advanced optical particle counting system that can detect nanoscale particles (e.g., less than 100 nm, more desirably less than 50 nm, and in some cases less than 20 nm) and that is compatible with multiple carrier fluid compositions.

[0007] BRIEF SUMMARY OF THE INVETION

[0008]

[0006] Provided herein is an optical particle analyzer or counter that accounts for and adjusts for the refractive index of the carrier fluid being analyzed, and related methods of use. The analyzer is robust and can be implemented in a variety of optical particle counters, including obscured light, reflected light, emitted light, and scattered light particle counters. The analyzer is useful with any fluid, including gases or liquids. In some cases, the analyzer can account for the difference in refractive index between two liquids, such as ultrapure water and an acid (e.g., sulfuric acid, hydrochloric acid, hydrofluoric acid, acetic acid, phosphoric acid, chromic phosphoric acid, etc.). The analyzer can be configured to account for the difference in refractive index between different fluids, including liquids and gases. By accounting for the refractive index of the carrier fluid, the described analyzer and method are also more sensitive and can more accurately and reliably detect and characterize smaller particles (e.g., nanoscale).

[0009]

[0007] By taking the refractive index into account, the described systems and methods can also optimize channel settings for particle characterization. Because the refractive index is known (e.g., by knowing the fluid composition and / or by measuring the refractive index with an instrument such as a refractometer), not only is particle detection improved, but the size or size range determined by the particle counter is more accurate.

[0010] In one aspect, the optical particle analyzer comprises: (i) a light source (e.g., laser or LED) for generating a beam of electromagnetic radiation; ii) a flow chamber for generating scattered or emitted electromagnetic radiation by flowing a fluid containing particles along a flow direction through the beam of electromagnetic radiation; (iii) an optical collection system for collecting and directing the scattered or emitted electromagnetic radiation from an observation region containing the particles (if present) onto a detector; and iv) a refractive index optimizer operatively connected in optical communication with one or more of the laser, the optical collection system or the detector to optimize collection of the electromagnetic radiation by the detector. In this manner, the refractive index optimizer is configured in combination with and controlled by other optical components to control the focus of the beam of electromagnetic radiation in the flowing fluid of the particles based on the refractive index of the flowing fluid and optimize collection of the electromagnetic radiation by the detector. Not only can the beam of electromagnetic radiation be properly focused on a desired observation region, including corresponding to a desired portion of the flow cell, but the radiation collected after interaction with the fluid sample can be properly focused on the detector, thereby enhancing the sensitivity, resolution, and / or accuracy of the particle analyzer.

[0011] The analyzers and methods described herein can rapidly and automatically account for refractive index changes in a number of ways. For example, the analyzer can have positioners or motors, or other means, for shifting the position or angle of any of the components, including the light source or optics, including the electromagnetic radiation collection system. The analyzer can also adjust the light source (e.g., laser) by changing the beam shape, beam position, or beam intensity. Each of these accounts for refractive index changes by optimizing the focus of the beam and collection / detection system, regardless of the fluid refractive index. The positioners or motors can be configured to provide positioning in the millimeter to micron range, e.g., positioning in the range of 10 mm to 0.1 μm. The amount of movement required will vary with the expected range of refractive index. For small differences where there is little difference in refractive index, small movements are required to achieve the desired optimization. Large differences require relatively large movements. Thus, various positioners or motors can be utilized, such as picomotor translation stages, rack-and-pinion worm gears, and / or linear actuators. Similarly, adjustment angles such as for mirrors, lenses, or light sources can range from 10° to 0.01°, using a rotary picomotor stage that can account for very small but significant refractive index differences between fluids.

[0012]

[0010] In an optical sense, the refractive index optimizer may be a beam shaping optical assembly positioned between an optical laser and a flow chamber, where the refractive index optimizer adjusts the beam shape or beam position of the electromagnetic radiation within the flow chamber to optimize the collection of the electromagnetic radiation.

[0013]

[0011] The refractive index optimizer can be operatively connected to the laser to adjust the position of the laser relative to the flow chamber to optimize the collection of electromagnetic radiation. The adjustment can be made by any means known in the art, for example, positioners such as electric motors, piezoelectric actuators, motion stages, micrometers, picometers, etc. can be used to reliably position optical components such as a light source including a laser. Adjusting the orientation of the laser then adjusts the direction of the electromagnetic radiation beam, thereby ensuring that the focal point of the beam intersects the observation window, taking into account the refractive index of the fluid (e.g., liquid or gas composition).

[0014]

[0012] The analyzers and methods described herein are also compatible with positioners or controllers that position or control optical components optically downstream of the light source. For example, instead of controlling the position of a light source, optical mirrors, lenses, etc. can be controlled via motors, positioners and / or actuators to vary (including the position) the beam of electromagnetic radiation.

[0015]

[0013] The refractive index optimizer is operatively connected to the collection system and can adjust the focal depth of the collection system relative to the flow chamber to optimize collection of electromagnetic radiation. This operative connection refers to controlling the lens position and / or the curvature or type of lens (including changing lenses or controlling lenses with controllable curvature).

[0016]

[0014] The refractive index optimizer is operably connected to the detector and can adjust the position of the detector relative to the flow chamber to optimize collection of electromagnetic radiation, such as by any one or more of a motor, positioner, or actuator.

[0017]

[0015] The refractive index optimizer can adjust the position of the laser, collection system, or detector in the x-axis, y-axis, z-axis, or any combination thereof. The refractive index optimizer can maximize the output signal from the detector.

[0018]

[0016] Various methods can be used to provide the analyzers described herein with the actual or estimated refractive index of the fluid being analyzed. The refractive index may be input by a user into an optical particle counter or refractive index optimizer, for example, where the refractive index is provided as a number, or where the fluid composition and / or concentration is provided and the refractive index is determined from a look-up table.

[0019] The analyzer and method may further include a refractometer operably connected to the flow chamber, more specifically to the fluid introduced into the flow chamber, and a refractive index optimizer, the refractometer providing the refractive index to the refractive index optimizer. The described analyzer and method may further include a processor operably connected to the optical particle counter and the refractive index optimizer, the optical particle counter functioning as the refractometer. The refractive index optimizer may optimize the collection of electromagnetic radiation at a refractive index selected from 1.3 to 1.6. The refractive index optimizer may provide contrast detection autofocus (CDAF) or phase detection autofocus (PDAF).

[0020] Any of the devices and methods provided herein preferably include a processor to facilitate automation of the device or method. For example, based on a known or measured refractive index input to the processor, the processor may determine the focus including sending control signals to a refractive index optimizer to control one or more incident light source positions and orientations, beam shapes, optical collection system configurations, and / or detector positions, thereby avoiding active user intervention. The "optical collection system configuration" may be represented by optical parameters including the positions / orientations of optical components of the optical collection system and / or the types of optical components such as lens type or lens shape.

[0021]

[0019] In one aspect, an optical particle analyzer including a counter comprises: i) a laser for generating a beam of electromagnetic radiation; ii) a flow chamber for generating scattered or emitted electromagnetic radiation by flowing a fluid containing particles along a flow direction through the beam of electromagnetic radiation; iii) an optical collection system for collecting and directing the scattered or emitted electromagnetic radiation from an observation region to a detector; and iv) a beam shaping optical assembly operably connected to the laser, which adjusts the beam shape or beam position of the electromagnetic radiation, characterized in that the beam shaping optical assembly adjusts the beam shape or beam position based on the refractive index of the fluid.

[0022]

[0020] The optical particle analyzer further comprises a refractometer operably connected to the flow chamber for determining the refractive index of the fluid, and further comprises a processor operably connected to the refractometer and a beam shaping optical assembly that adjusts the beam shape or beam position based on the refractive index determined by the refractometer.

[0023] In one aspect, a method of maximizing a signal output of an optical particle counter includes the steps of: i) providing an optical particle counter comprising: a) a laser for generating a beam of electromagnetic radiation, b) a flow chamber for generating scattered or emitted electromagnetic radiation by flowing a particle-laden fluid along a flow direction through the beam of electromagnetic radiation, c) an optical collection system for collecting and directing the scattered or emitted electromagnetic radiation from an observation region to a detector, and d) a beam shaping optical assembly operatively connected to the laser, ii) measuring a refractive index of the fluid in the flow chamber, and iii) adjusting at least one of the following: the beam shaping optical assembly to a beam shape and / or beam position of the electromagnetic radiation entering the flow chamber based on the measured refractive index, or the position of either the laser, the optical collection system, the detector, or any combination thereof based on the measured refractive index to optimize a focal depth of the electromagnetic radiation entering the flow chamber and provided to the detector, thereby increasing the amount of electromagnetic radiation reaching the detector and maximizing the signal output of the optical particle counter.

[0024]

[0022] The refractive index can be measured automatically by a refractometer operably connected to the fluid. This aspect is preferred when the user does not need to determine the fluid composition or when the fluid composition can change over time, including batch-to-batch variations or instruments that typically encounter different fluid compositions. In other words, the refractive index can be a time-varying refractive index, and the fluid composition can change sufficiently over time that the refractive index changes over time, depending on the intended application.

[0025]

[0023] However, this method is compatible with the refractive index being determined manually by introducing a fluid having a known refractive index into the flow chamber. For example, if a user is provided with a fluid composition, the refractive index of that fluid is looked up instead of measured, with the corresponding input into the particle analyzer of the refractive index optimizer. Thus, the method may further include the steps of determining the refractive index value by a lookup table and manually inputting the refractive index value into the particle analyzer.

[0026]

[0024] The method may further include adjusting the beam shaping optical assembly to provide an optimized beam shape and / or beam position of the electromagnetic radiation entering the flow chamber based on the refractive index.

[0027]

[0025] The method may further include adjusting the position of the laser, the light collection system, the detector, or any combination thereof.

[0028]

[0026] In one aspect, a method for maximizing a signal output of an optical particle counter includes the steps of: i) preparing an optical particle counter comprising: a) a laser for generating a beam of electromagnetic radiation; b) a flow chamber for generating scattered or emitted electromagnetic radiation by flowing a fluid containing particles along a flow direction through the beam of electromagnetic radiation; and c) an optical collection system for collecting the scattered or emitted electromagnetic radiation from an observation region and directing it to a detector; ii) measuring the refractive index of the fluid in the flow chamber; and iii) adjusting the position of the laser, the optical collection system, the detector, or any combination thereof, to optimize the focal depth of the electromagnetic radiation entering the flow chamber, thereby increasing the amount of electromagnetic radiation reaching the detector and maximizing the signal output of the optical particle counter.

[0029]

[0027] While not wishing to be bound by any particular theory, a belief or understanding of the underlying principles relating to the devices and methods disclosed herein may be explained herein. It is recognized that regardless of the ultimate accuracy of any mechanistic explanation or hypothesis, embodiments of the present invention may nevertheless be effective and useful. [Brief description of the drawings]

[0030] [Figure 1] FIG. 1 illustrates an integrated refractive index optimizer and optical particle counter. [Diagram 2] FIG. 2 is a top view of the particle counter with the flow direction perpendicular to the plane of observation. [Diagram 3] Figure 3 compares particles detected by optical counting in sulfuric acid. The left column represents the number of particles detected using a particle counter specifically calibrated to detect in a high refractive index (~1.6), while the right represents analysis of the same fluid using a particle counter calibrated to detect particles in a low refractive index fluid such as water (~1.3). The difference in magnitude reflects that counting is severely and significantly affected when the refractive index of the carrier fluid is not taken into account. Detailed Description of the Invention

[0031]

[0031] Generally, the terms and phrases used herein have their art-recognized meanings, which can be found by reference to standard texts, journal references, and contexts known to those of skill in the art. The following definitions are provided to clarify their specific use in the context of the present invention.

[0032]

[0032] "Refractive index optimizer" refers to a system or subsystem in an optical particle counter that allows the focal point of the particle counter to be shifted based on the refractive index of the carrier fluid being analyzed by the particle counter. The refractive index optimizer can use motors, electronics, other motion systems, or a series of such motion systems to adjust the position or angle of one or more optical systems (e.g., light source, collection system, detector, beam shaping system, etc.) relative to the flow cell. The refractive index optimizer may also adjust the beam shaping system, and the light source may change the beam shape, beam intensity, or beam target within the flow cell. The refractive index optimizer can include a control unit, one or more motors, a display, an input (e.g., a keyboard or touch screen, or a data link to another device such as a computer or smartphone), a processor, and / or a refractometer.

[0033]

[0033] "Flow direction" refers to the axis parallel to the direction in which the majority of the fluid moves when the fluid is flowing. For fluid flowing through a straight flow cell, the flow direction is parallel to the path taken by the majority of the fluid. For fluid flowing through a curved flow cell, the flow direction can be considered to be tangential to the path taken by the majority of the fluid.

[0034] "Optical communication" refers to components arranged so that light or electromagnetic radiation is transmitted between the components.

[0035]

[0035] "Optical components" is used broadly herein to refer to components useful for generating, controlling / directing, and detecting electromagnetic radiation, specifically electromagnetic radiation that has been introduced into a fluid sample and interacted with the fluid, including any particles suspended in the fluid. Examples include mirrors, lenses, and filters.

[0036]

[0036] "Operably connected" is used broadly herein to refer to an arrangement of elements such that the action or reaction of one element affects another, but preserves the functionality of each element. For example, the term can include elements that communicate optically with each other and do not necessarily physically contact each other. For example, a refractive index optimizer operably connected to a light source, such as a laser, can include elements such as mirrors, lenses, filters, or other optical components that affect one or more characteristics of the light beam output, but do not directly control the laser itself. Similarly, a refractive index optimizer operably connected to a detector can include control of the output beam to ensure that it is properly directed to the detector. Of course, operably connected also includes aspects where there is a more direct physical interconnection, such as a refractive index optimizer that includes a positioner that effects physical movement of the laser, detector, and / or components of the light collection system.

[0037]

[0037] "Positioner" is used broadly to refer to any known means in the art for reliably moving components, including down to the micron level, in a reliable and repeatable manner. Examples include, but are not limited to, electric motors, piezoelectric actuators, spring-loaded drives, micrometer-driven positioning stages, and micrometers. The systems and methods provided herein are compatible with manually or automatically controlled positioners. A user or a processor can be used to place an optical component in a desired position as long as the refractive index is known.

[0038]

[0038] "Light source" refers to a device or device component capable of delivering electromagnetic radiation to a sample. The term is used broadly to include any electromagnetic radiation, and is not limited to visible light, such as by a visible light beam. The light source may be embodied as a laser or laser array, such as a diode laser, a diode laser array, a diode laser pumped solid-state laser, an LED, an LED array, a gas phase laser, a solid-state laser, or a combination thereof. Unless otherwise noted, the term "light laser" is substituted.

[0039] The terms "electromagnetic radiation" and "light" are used interchangeably herein and refer to waves of electric and magnetic fields. Electromagnetic radiation useful in the methods of the present invention includes, but is not limited to, ultraviolet light, visible light, infrared light, or any combination having wavelengths between about 100 nanometers (nm) and about 15 microns (μm).

[0040]

[0040] The phrase "detecting a particle" broadly refers to sensing, identifying the presence of a particle, and / or characterizing a particle. In some embodiments, detecting a particle refers to counting the particles. In some embodiments, detecting a particle refers to characterizing and / or measuring a physical property of a particle, such as particle size, cross-sectional dimension, shape, size, aerodynamic size, or any combination thereof.

[0041]

[0041] "Particle" refers to a small object that is often considered a contaminant. A particle may be any material that is generated by the action of friction, for example, when two surfaces are in mechanical contact and there is mechanical movement. A particle may be composed of aggregates of material such as dust, dirt, smoke, ash, water, soot, metals, minerals, or any combination of these or other materials or contaminants. "Particle" may also refer to biological particles, such as viruses, spores, and microorganisms, including bacteria, fungi, archaea, protists, other single-celled microorganisms, and particularly microorganisms having a size on the order of 1-15 μm. A particle may refer to any small object that absorbs or scatters light and is therefore detectable by an optical particle counter. As used herein, "particle" is intended to exclude individual atoms or molecules of a carrier fluid, such as water molecules, process chemical molecules, oxygen molecules, helium atoms, nitrogen molecules, etc. The systems and methods can detect, size, and / or count particles, including aggregates of material having sizes of 10 nm, 20 nm, 30 nm, 50 nm, 100 nm, 500 nm, 1 μm or greater, or 10 μm or greater, including particles between 20 nm and 50 nm, between 50 nm and 50 μm, between 100 nm and 10 μm, and between 500 nm and 5 μm.

[0042]

[0042] The terms "optical liquid particle counter" and "particle counter" are used interchangeably herein and refer to a system capable of detecting particles suspended in a liquid, determining the size of particles suspended in a liquid, counting particles suspended in a liquid, classifying particles suspended in a liquid, or any combination thereof. A typical optical liquid particle counter is composed of several components, such as a source for generating a beam of electromagnetic radiation, optics for directing the beam into a region in which a fluid sample flows, such as a liquid or gas flowing through a flow cell. A typical optical liquid particle counter also includes a photodetector, such as a two-dimensional photodetector, collection optics for detecting electromagnetic radiation obscured, scattered, or emitted by particles passing through the beam, and other electronics for processing and analyzing the electrical signal generated by the photodetector, including a current-to-voltage converter and signal filtering and amplification electronics. The optical particle counter may also include a pump for generating a flow for introducing a liquid sample into a detection region in which the electromagnetic beam is present.

[0043]

[0043] "Fluid communication" refers to an arrangement of two or more objects where a fluid is transported to, through, or from one object to another. For example, in some embodiments, two objects are in fluid communication with one another if a fluid flow path is provided directly between the two objects. In some embodiments, two objects are in fluid communication with one another if a fluid flow path is provided indirectly between the two objects, such as by the inclusion of one or more other objects or a flow path between the two objects. In one embodiment, two objects present within a body of fluid are not necessarily in fluid communication with one another unless fluid from the first object is drawn to, passes through, and / or passes through the second object, e.g., along a flow path.

[0044] The following examples further illustrate the invention but, of course, should not be construed as in any way limiting its scope. Example 1

[0045]

[0045] This example illustrates an optical particle counter that includes a refractive index optimizer that adjusts various aspects of the system (e.g., component positioning, beam characteristics) to ensure that the focal point of the system is positioned within tolerances and that the data it generates is accurate. In these systems, the refractive index optimizer is an active design element that ensures that electromagnetic radiation is collected and then collected or expanded onto a detector from an ideal measurement point within the sample or flow cell.

[0046]

[0046] Variations in the refractive index of the fluid cause shifts in the optical system focus within the measurement cell that can affect the shape and position of the beam, as well as the area within the cell where light is collected and properly collected onto the detector. These variations, individually or in combination, affect the performance of the particle counter in several ways.

[0047] An integrated refractive index optimizer and optical particle counter is provided in FIG. 1. As shown by the dotted lines, the refractive index optimizer 101 is operatively connected to one or more of a light source 220, a light collection system 230, a detection system 240, a refractometer 102, and / or a beam shaping optical assembly 203. The liquid particle counter 100 is provided in fluid communication with a liquid conduit 150 such that a liquid having particles 31 flows through a flow chamber 210 of the particle counter. A light source 220, such as a laser or light emitting diode, generates a beam of electromagnetic radiation 221 that passes through the flow chamber 210 and interacts with the particles as they pass through the flow chamber at an observation region 211 that includes a focal point for a particular fluid in the flow chamber 210. The transmitted, scattered or emitted electromagnetic radiation is collected by a collection system 230 and directed to a detector system 240 that generates an electrical signal corresponding to the particle or a property of the particle passing through the flow cell.

[0048]

[0048] The refractive index optimizer may be used to control the focal depth 231 so that the transmitted light from the collection system 230 is ideally focused on a plane corresponding to the detector elements of the detector system 240, thereby further optimizing the collection of electromagnetic radiation scattered or emitted by the particles 31 in the flowing fluid 30. The focal depth is controlled by any of a variety of means known in the art, including adjusting the position of one or more optical components in any one or more of the x, y and z directions, as well as by the collection lens and the curvature of such lens. Similarly, the actual detector 240 may be moved so that the position of the detection plane of the detector corresponds to the focal depth 231.

[0049]

[0049] Figure 1 is a schematic diagram illustrating shielding or exclusion of a liquid particle counter. However, the concepts and embodiments described herein are also applicable to other types of particle counters, including scattered light or emitted light particle counters. Figure 2, for example, shows a configuration of a scattered liquid particle counter, where the detection system is offset (e.g., by 90 degrees) from the path of the electromagnetic radiation 221 from the light source 220. Figure 2 provides a top view of the liquid particle counter, where the flow direction is orthogonal to the plane of observation. In this respect, a fluid monitoring system provided either upstream or downstream of the flow chamber 210 is not shown in Figure 2.

[0050]

[0050] As shown in Fig. 1, the refractive index optimizer 101 can adjust the change in refractive index in many different ways. For example, one or more of the light source 220, the light collection system 230, and / or the detector 240 can include motors or other position changing means relative to the other components, so that the focus of the system can be adjusted by the refractive index optimizer 101 when a change in refractive index is input or detected. The analyzer can adjust the position or orientation of various components, either offline or online, including shifting the X-axis, Y-axis, or Z-axis and / or rotating one or more components of the optical assembly about these axes, relative to the ideal focus (measurement) point of the flow cell 210. The refractive index optimizer 101 may be operatively connected to the light source 220 or the optical components (e.g., beam shaping optical system) 203, and the refractive index optimizer 101 may adjust the beam shape, beam intensity, or beam position. The particle counter can have separate positions pre-calibrated for various common fluids or refractive indices.

[0051]

[0051] The refractive index optimizer 101 can be updated with changes in the refractive index of the carrier fluid in several ways. For example, the refractive index optimizer can include a processor 103 and utilize data received from the detector 240 or other components to calculate or estimate the refractive index of the fluid. The refractive index optimizer 101 may have an input and / or display or be operatively connected to the input and / or display of the particle counting system 100, where a user or input inputs the refractive index of the fluid, or the chemical composition and / or concentration of the fluid, and the refractive index optimizer 101 then uses a look-up table or algorithm to determine the refractive index. A refractometer 102 (or similar device) may be provided in fluid communication with the carrier fluid (ether via conduit 150 or flow chamber 210) and in data communication with the refractive index optimizer 101. The refractometer 102 can provide the calculated or estimated refractive index to the refractive index optimizer 101, for example in real time. The refractometer 102 also provides a signal, via data communication, to the refractive index optimizer 101, which then interprets or calculates the refractive index of the fluid.

[0052]

[0052] In addition, the described system and method may utilize an autofocus method to adjust for changes in the refractive index of the carrier fluid. In general, a laser is used to generate a beam of electromagnetic radiation. Particles along the fluid flow path flow through the electromagnetic radiation, as do the molecules of the flowing fluid itself. When the scattered light collection and focusing optics are aligned to a fluid with a known refractive index, the root mean square spot size, and therefore an image of the scattered light of either the particles or molecules, is focused onto the detector. The molecular scattering of the fluid caused by the impinging laser produces an image of the electromagnetic radiation of the laser inside the fluid itself, which is imaged by the system detector. This laser image can be analyzed with an autofocus method. When applying multidimensional array detection, autofocus can be achieved, for example, by contrast detection autofocus (CDAF) or phase detection autofocus (PDAF) methods. In single or individual detection, changes in the sample fluid change the refractive index, causing a defocusing of the image on the detector and a loss of collected incident power. These autofocus methods and power losses can be real-time output information to a refractive index optimizer to reshape both the laser beam and the scattered light collection through optical lens assembly movement to refocus and maximize the power of both the laser's electromagnetic radiation and the particle scattered radiation.

[0053]

[0053] Figure 3 compares particles detected by optical particles in sulfuric acid. The left side of the graph represents the number of particles detected using a particle counter specifically calibrated to detect at a high refractive index (~1.6), while the right side represents an analysis of the same fluid using a particle counter calibrated to detect particles in fluids with a low refractive index (~1.3) such as water. Figure 3 shows that in this example, using a particle counter that is not calibrated to account for the refractive index results in a reduced detection capability for the higher refractive index.

[0054] INCORPORATION-BY-REFERENCE AND MODIFICATION STATEMENT

[0055]

[0054] All references cited herein, including publications, patent applications, and patents, are incorporated by reference into this document as if each reference was individually and specifically indicated to be incorporated by reference and was set forth in its entirety herein.

[0056] In the context of describing the invention (particularly in the context of the claims which follow), use of the terms "a," "an," "the," and "at least one" and similar referents should be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. Use of the term "at least one" followed by a list of one or more items (e.g., "at least one of A and B") should be construed to mean one item selected from the listed items (A or B), or any combination of two or more of the listed items (A and B), unless otherwise indicated herein or clearly contradicted by context. The terms "comprising," "having," "including," and "including" should be construed as open-ended terms (i.e., meaning "including but not limited to"), unless otherwise indicated. The recitation of ranges of values ​​herein is merely intended to serve as a shorthand method of individually referencing each of the independent values ​​within the ranges, unless otherwise indicated herein, and each independent value is incorporated herein as if it were individually recited herein. All methods described herein can be performed in any suitable order, unless otherwise indicated herein or clearly contradicted by context. The use of any and all examples or exemplary language (e.g., "etc.") provided herein is intended merely to better clarify the invention, and does not limit the scope of the invention unless specifically claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.

[0057]

[0056] Preferred embodiments of the invention are described herein, including the best mode known to the inventors for carrying out the invention. Variations of these preferred embodiments will become apparent to those skilled in the art upon reading the foregoing description. The inventors expect that those skilled in the art will employ such variations as appropriate, and the inventors intend to practice the invention other than as specifically described herein. Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is covered by the invention unless otherwise indicated herein or clearly contradicted by context.

[0058]

[0057] All references throughout this application, e.g., patent documents, including issued or granted patents or equivalents, patent application publications, and non-patent documents or other source materials, are incorporated by reference in their entirety into this application, as if each reference were individually incorporated by reference, unless each reference is at least partially inconsistent with the disclosure of this application (e.g., a partially inconsistent reference is incorporated by reference except for the partially inconsistent portion of the reference).

[0059]

[0058] The terms and expressions used herein are used as terms of description and not as terms of limitation, and there is no intention in the use of such terms and expressions to exclude the equivalents of the features shown and described or parts thereof, but it is recognized that various modifications are possible within the scope of the claimed invention. Thus, although the present invention has been specifically disclosed by preferred embodiments, exemplary embodiments, and optional features, it should be understood that modifications and variations of the concepts disclosed herein are accessible by those skilled in the art, and such modifications and variations are considered to be within the scope of the present invention as defined by the appended claims. The specific embodiments provided herein are examples of useful embodiments of the present invention, and it will be apparent to those skilled in the art that the present invention can be implemented using numerous variations of the devices, device components, and method steps described herein. As will be apparent to those skilled in the art, the methods and devices useful for the methods can include numerous optional compositions and processing elements and steps.

[0060]

[0059] When a permutation group is disclosed herein, it is understood that all individual members and all subgroups of that group are separately disclosed. When a Markush or other group is used herein, all individual members of the group, and all possible combinations and subcombinations of the group, are intended to be included individually in the disclosure.

[0061]

[0060] Unless otherwise specified, the invention can be practiced using any arrangement or combination of the components described or illustrated herein.

[0062]

[0061] Whenever a range is described in the specification, e.g., a temperature range, a refractive index range, or a composition or concentration range, all intermediate and subranges, as well as all individual values ​​contained within the described range, are intended to be included in the disclosure. It will be understood that any subrange or individual value within a range or subrange described herein can be excluded from the claims herein.

[0063] All patents and publications mentioned in the specification are indicative of the level of skill of those skilled in the art to which the present invention pertains. References cited herein are incorporated by reference in their entirety to indicate the state of the art at the date of their publication or filing, and this information is intended to be used herein to exclude certain embodiments that are in the prior art, if necessary. For example, when a composition is claimed, it should be understood that compounds that are known and available in the art prior to the applicant's invention, including compounds for which enabling disclosures are provided in the references cited herein, are not intended to be included in the composition claims herein.

[0064]

[0063] As used herein, "comprising" is synonymous with "including," "including," or "characterized by," and is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. As used herein, "consisting of" excludes any element, step, or ingredient not specified in the claim element. As used herein, "consisting essentially of" does not exclude materials or steps that do not materially affect the basic and novel characteristics of the claim. In each example herein, any of the terms "comprising," "consisting essentially of," and "consisting of" may be replaced with any of the other two terms. The invention illustratively described herein may suitably be practiced in the absence of any element, limitation, or restriction not specifically disclosed herein.

[0065]

[0064] Those skilled in the art will understand that starting materials, biological materials, reagents, synthesis methods, purification methods, analysis methods, assembly methods, and biological methods other than those specifically exemplified can be used in the practice of the present invention without resorting to undue experimentation. All known functional equivalents of such materials and methods are intended to be included in the present invention. The terms and expressions used are used as terms of description and not as terms of limitation, and there is no intention in the use of such terms and expressions to exclude any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the claimed invention. Thus, although the present invention has been specifically disclosed by preferred embodiments and optional features, it should be understood that modifications and variations of the concepts disclosed herein are accessible to those skilled in the art, and such modifications and variations are considered to be within the scope of the present invention as defined by the appended claims.

Claims

1. In optical particle analyzers, a light source for generating a beam of electromagnetic radiation; a flow chamber for generating scattered or radiated electromagnetic radiation by flowing a particle-containing fluid along a flow direction through a beam of electromagnetic radiation; a light collection system that collects and directs the scattered or emitted electromagnetic radiation from the observation region to a detector; a refractive index optimizer operatively connected to one or more of the light source, the light collection system, or the detector to control a focus of the beam of electromagnetic radiation in the flowing fluid of particles based on the refractive index of the flowing fluid and to optimize collection of the electromagnetic radiation by the detector; 1. An optical particle analyzer comprising:

2. 10. The optical particle analyzer of claim 1, wherein the refractive index optimizer comprises a beam shaping optical assembly optically disposed between the light source and the flow chamber, the refractive index optimizer adjusting a beam shape or beam position of the electromagnetic radiation within the flow chamber.

3. 3. The optical particle analyzer of claim 1 or 2, wherein the refractive index optimizer comprises a positioner and / or optical components operatively connected to the light source for adjusting the direction of the beam of electromagnetic radiation generated by the light source, the light source being a laser.

4. 4. The optical particle analyzer of claim 3, wherein the refractive index optimizer comprises a positioner that moves the laser or moves the optical components that control the direction and / or shape of the beam of electromagnetic radiation output by the laser.

5. 5. The optical particle analyzer of claim 1, wherein the refractive index optimizer is operably connected to the light collection system and adjusts a focal depth of the collection system relative to the flow chamber to correspond to a position of the detector.

6. 6. The optical particle analyzer of claim 1, wherein the refractive index optimizer comprises a positioner operatively connected to the detector for adjusting the position of the detector relative to the flow chamber.

7. 10. The optical particle analyzer of claim 1, wherein the refractive index optimizer comprises a positioner that adjusts a three-dimensional position of one or more of the light source, the collection system, or the detector in one or more of an x-axis, a y-axis, or a z-axis.

8. 8. The optical particle analyzer of claim 1, wherein the refractive index optimizer is configured to position one or more of the light source, the light collection system, or the detector to maximize an output signal from the detector based on the refractive index of a fluid.

9. An optical particle analyzer according to any one of claims 1 to 8, wherein the refractive index is input into the optical particle analyzer or the refractive index optimizer by a user.

10. a refractometer operably connected to the flow chamber and the refractive index optimizer; An optical particle analyzer according to any preceding claim, wherein the refractometer measures the refractive index and provides the refractive index to the refractive index optimizer.

11. a processor operatively connected to the refractometer and the refractive index optimizer; The processor, determining said focal point based on the measured refractive index; 11. The optical particle analyzer of claim 10, configured to send control signals to the refractive index optimizer to control one or more of a direction of the beam of electromagnetic radiation, optical parameters of the light collection system, or a position of the detector to optimize collection of the electromagnetic radiation by the detector.

12. The optical particle analyzer of any one of claims 1 to 11, wherein the refractive index optimizer is configured to provide contrast detection autofocus (CDAF) or phase detection autofocus (PDAF).

13. An optical particle analyzer according to any preceding claim, wherein the flowing fluid has a refractive index selected from the range of 1.3 to 1.

6.

14. a laser for generating a beam of electromagnetic radiation; a flow chamber configured to generate scattered or emitted electromagnetic radiation by flowing a particle-containing fluid along a flow direction through a beam of electromagnetic radiation at an observation region; a light collection system; a detector in optical communication with the light collection system, the light collection system collecting the scattered or emitted electromagnetic radiation from the observation region and directing it onto the detector; a beam shaping optical assembly operatively connected to the laser, the beam shaping optical assembly adjusting a beam shape or a beam position of the electromagnetic radiation; 1. An optical particle analyzer comprising: The beam shaping optical assembly adjusts the beam shape or the beam position based on the refractive index of the fluid.

15. a refractometer operably connected to the flow chamber for measuring the refractive index of the fluid; a processor operatively connected to the refractometer and the beam shaping optical assembly; Further comprising: The processor, determining an optimal beam shape and / or beam position based on the refractive index; 15. The optical particle analyzer of claim 14, wherein the beam shaping optical assembly is controlled to optimize the beam shape and / or position.

16. An optical particle analyzer according to any one of claims 14 to 15, wherein the refractive index optimizer is configured to provide contrast detection autofocus (CDAF) or phase detection autofocus (PDAF).

17. 1. A method for maximizing a signal output of an optical particle counter, comprising: The optical particle analyzer comprises: a laser for generating a beam of electromagnetic radiation; a flow chamber for generating scattered or radiated electromagnetic radiation by flowing a particle-containing fluid along a flow direction through a beam of electromagnetic radiation; a light collection system that collects and directs the scattered or emitted electromagnetic radiation from the observation region to a detector; a beam shaping optical assembly operatively connected to the laser; Equipped with The method comprises: Providing an optical particle analyzer; flowing a fluid through a flow chamber; measuring the refractive index of the fluid in the flow chamber; adjusting one of the beam shaping optical assembly relative to a beam shape and / or beam position of the electromagnetic radiation entering the flow chamber based on the measured refractive index, or the position of the laser, the light collection system, the detector, or any combination thereof based on the measured refractive index to optimize a focal depth of the electromagnetic radiation entering the flow chamber and / or the electromagnetic radiation provided to the detector; Including, This increases the amount of electromagnetic radiation reaching the detector and maximizes the signal output of the optical particle counter.

18. 20. The method of claim 17, wherein the refractive index is measured automatically by a refractometer operably connected to the fluid.

19. 20. The method of claim 18, wherein the refractive index is a time-varying refractive index.

20. The method of claim 17 , wherein the refractive index is determined manually by introducing a fluid having a known refractive index into the flow chamber.

21. 21. The method of claim 20, further comprising determining the refractive index value by a look-up table and manually entering the refractive index value into the optical particle analyzer.

22. The method of any one of claims 17 to 21, further comprising adjusting the beam shaping optical assembly to a beam shape and / or beam position of the electromagnetic radiation entering the flow chamber.

23. The method of any one of claims 17 to 21, further comprising adjusting the position of the laser, the light collection system, the detector, or any combination thereof.

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