Advanced systems and methods for interference particle detection and detection of particles having small size dimensions - Patents.com

Abstract

The present invention relates to the interferometric detection of particles and the optical detection of particles having size dimensions of 100 nm or less. Systems and methods are provided that exhibit a high degree of alignment and stability for the interferometric detection of particles and / or the optical detection of particles having size dimensions of 100 nm or less. Systems and methods are provided that include compensation means to mitigate the effects of internal and external stimuli and changes in operating conditions that may reduce the sensitivity and reliability of particle detection by optical methods, including interferometric-based techniques and / or systems for the optical detection of particles having size dimensions of 100 nm or less.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001]

[0001] This application claims the benefit of and priority to U.S. Provisional Patent Application No. 62 / 939,232, filed November 22, 2019, which is incorporated herein by reference. [Background technology]

[0002]

[0002] Technological and industrial advances requiring cleanroom conditions have resulted in the need for detection and characterization of increasingly small particles. For example, microelectronics foundries seek to detect particles less than 20 nm in size, and in some cases less than 10 nm in size, because particles of these dimensions can affect increasingly sensitive manufacturing processes and products. Similarly, the need for sterile processing conditions for the manufacture of pharmaceuticals and biomaterials requires accurate characterization of viable and non-viable particles to address compliance standards related to health and human safety.

[0003]

[0003] Typically, these industries rely on optical particle counters for the detection and characterization of small particles. To be able to detect smaller particles, new approaches to optical particle counting are required, such as systems employing increased laser power, shorter excitation wavelengths, and more complex techniques such as condensation nucleus counting, which can dramatically increase the cost and overall complexity of devices capable of detecting nanometer-scale particles. These new approaches can also require more frequent calibration and maintenance to provide the necessary reliability and reproducibility.

[0004]

[0004] Various optical particle counters are known in the art, for example, scattered light optical particle counters are provided in U.S. Patent No. 7,916,293, and transmission / extinction particle counters, including those utilizing structured beams and / or interferometry, are provided in U.S. Patent No. 7,746,469, U.S. Patent No. 9,983,113, U.S. Patent No. 10,416,069, U.S. Patent Application Publication No. 2019 / 0277745, U.S. Patent Application Publication No. 20170176312, and PCT Publication No. WO 2019 / 082186. Each of these cited references is incorporated herein in its entirety, and specifically incorporated to describe the components and configurations of particle counter systems useful for detecting and characterizing small particles.

[0005]

[0005] From the foregoing, there is a need in the art for systems and methods that provide advanced optical sensing of particles having small size dimensions. Summary of the Invention

[0006] The present invention relates to interference detection of particles and optical detection of particles having size dimensions of 100 nm or less. Systems and methods are provided that exhibit high degree of alignment and stability for interference detection of particles and / or optical detection of particles having size dimensions of 100 nm or less. Systems and methods are provided that include compensation means to mitigate the effects of internal and external stimuli and changes in operating conditions that may reduce the sensitivity and reliability of particle detection by optical methods, including interference-based techniques and / or systems for optical detection of particles having size dimensions of 100 nm or less. In embodiments, for example, the systems and methods are provided with active and / or passive components such as controllers, isolators and / or compensators that increase the operating tolerance of the optical particle detection system or method, including interference particle detection system or method and / or system for optical detection of particles having size dimensions of 100 nm or less. The system is useful for mitigating degradation in performance of optical particle counters and / or interferometric particle counters, such as those involving structured beam or heterodyne interferometric detection, for measuring particles having size dimensions of 100 nm or less with respect to aspects of the operating state or conditions, such as internal or external sources of vibration, sound waves, thermal energy, or changes in ambient and / or operating conditions, such as temperature, pressure, etc.

[0007]

[0007] In one aspect, a particle detection system comprises a flow cell for flowing a fluid containing particles; a light source for generating one or more beams of electromagnetic radiation, such as one or more coherent beams of electromagnetic radiation; beam shaping optics for generating electromagnetic radiation that is scattered by the particles by passing the one or more beams of electromagnetic radiation through the flow cell; and at least one optical detector array for receiving the electromagnetic radiation from the flow cell, wherein the light source, beam shaping optics, and optical detector array are configured to enable interferometric detection of particles and / or optical detection of at least one and optionally all of particles having size dimensions of 100 nm or less, and the system is configured such that at least one of temperature, pressure, degree of vibration, and degree of sonication, or any combination thereof, are each independently maintained within selected tolerances to maintain a high signal-to-noise ratio during detection of the particles, such as by interferometric detection of particles and / or optical detection of particles having size dimensions of 100 nm or less.

[0008]

[0008] In some embodiments, the systems and methods are for detecting particles smaller than 100 nm and use scattering-based methods or systems, fluorescence-based methods or systems, optical extinction-based methods or systems, interference-based methods or systems, condensation nucleus counting (CNC)-based methods or systems, and / or any combination thereof.

[0009] In one embodiment, the light source, beam shaping optics, and optical detector array are configured to perform structured beam interferometric detection of particles by passing a structured probe beam of coherent electromagnetic radiation through a flow cell. In one embodiment, the light source, beam shaping optics, and optical detector array are configured to perform heterodyne interferometric detection of the particles by collecting off-axis scattered light and combining the off-axis scattered light with a reference beam to form an interference signal. In one embodiment, the light source and optical detector array are configured to perform single or multi-beam interferometric detection of particles, including common path or differential path interferometry. In one embodiment, the light source and optical detector array are configured to perform structured dark beam interferometric detection of particles, such as a structured dark beam characterized by a spatial intensity profile having a region of attenuated intensity, such as a centerline decrease in intensity. In one embodiment, the light source and optical detector array are configured to perform Gaussian or non-Gaussian beam interferometric detection of the particles, for example by detection of both electromagnetic radiation transmitted through the flow cell and electromagnetic radiation scattered by the particles, in some instances resulting in a self-correcting interferometric geometry that offers the advantage of being less sensitive to thermal effects that may alter the beam path length.

[0010] In one embodiment, an optical detector array is disposed in optical communication with the flow cell to receive incident electromagnetic radiation transmitted through the flow cell and electromagnetic radiation scattered by the particles, e.g., where the electromagnetic radiation scattered by the particles includes forward scattered electromagnetic radiation. In one embodiment, the incident electromagnetic radiation passing through the flow cell and the electromagnetic radiation scattered by the particles undergo constructive and / or destructive optical interference, e.g., to generate one or more diffraction patterns. In one embodiment, the optical detector array is disposed at a scattering angle in the range of 0 degrees to 5 degrees relative to the optical axis of the incident beam, optionally in some applications at a scattering angle in the range of 0 degrees to 1 degree relative to the optical axis of the incident beam, optionally in some applications at a scattering angle in the range of 0 degrees to 0.5 degrees relative to the optical axis of the incident beam, optionally in some applications at a scattering angle in the range of 0 degrees to 0.1 degrees relative to the optical axis of the incident beam. In one embodiment, the optical detector array is disposed in optical communication with the flow cell to detect interactions of the particles and the electromagnetic radiation scattered by the particles with the illuminating wavefront. In one embodiment, an optical detector array is provided for differential detection.

[0011] The system and method of the present invention provides interference detection and / or optical detection of particles having size dimensions of 100 nm or less with improved tolerance to internal or external stimuli and changes in ambient and / or operating conditions. In one embodiment, the system is designed to withstand the following conditions: temperature (T) change of up to 5° C. at a rate of less than 1° C. / hr, pressure (P) change of up to 300 mbar, beam path length change of up to 10 mm, beam focus position change of up to 2 mm, beam power change of up to 20%, vibration level l of up to 200 microns / sec, beam angle change of up to + / - 5 degrees, laser noise condition of up to <2% (RMS), laser M of up to <1.3. 2The present invention provides interference detection of particles and / or optical detection of particles having size dimensions of 100 nm or less without significant performance degradation of the internal particle counting process when exposed to one or more of: changes in temperature, changes in laser linewidth up to <100 MHz, changes in RH up to <50%, electrical (line power) stability and noise control.

[0012]

[0012] Certain embodiments of the system and method include a controller component capable of maintaining sufficient alignment and stability during operation to perform accurate interference detection of particles in the fluid flow and / or optical detection of particles in the fluid flow having size dimensions of 100 nm or less. In one embodiment, the system further comprises a controller operably coupled to the flow cell, the light source, the beam shaping optics, the optical detector array, or any combination thereof, the controller for compensating for changes in the system parameters in response to ambient conditions, internal stimuli, external stimuli, or any combination thereof. In one embodiment, the ambient conditions, internal stimuli, or external stimuli are selected from the group consisting of changes in temperature, changes in pressure, vibrations, sound waves, or any combination thereof.

[0013] In one embodiment, the controller is a beam alignment system for monitoring the position of one or more beams and actively controlling the positioning and / or alignment of the flow cell, the light source, the beam shaping optics, the optical detector array, or any combination thereof to maintain a high signal-to-noise ratio during interference detection of particles and / or optical detection of particles having size dimensions of 100 nm or less. In one embodiment, the beam alignment system provides compensation for thermal expansion optical drift. In one embodiment, the beam alignment system provides low frequency vibration compensation. In one embodiment, the beam alignment system provides real-time control of the positioning and / or alignment of the flow cell, the light source, the beam shaping optics, the optical detector array, or any combination thereof within a range of 5 microradians or less at a frequency of 250 Hz or more.

[0014] In one embodiment, the beam alignment system is a closed-loop system capable of generating / receiving inputs and outputs for actively maintaining alignment and / or stability during interferometric detection of particles and / or optical detection of particles having size dimensions of 100 nm or less. In one embodiment, the one or more optical sensors are orthogonal optical sensors (e.g., positioned behind a folding mirror of the system) and the actuator system comprises one or more piezoelectrically actuated nanopositioners. In one embodiment, the optical sensors provide inputs to the closed-loop system and the actuator system provides outputs to maintain and stabilize the optical alignment during operation.

[0015] In one embodiment, the controller is an isolator or isolators for isolating the flow cell, the light source, the beam shaping optics, the optical detector array from changes in ambient conditions, internal stimuli, external stimuli of the operating environment, or any combination thereof. In one embodiment, the isolator is a vibration damping component capable of at least partially preventing the transmission of vibrations from the external operating environment to the system. In one embodiment, the isolator is a vibration damping component capable of at least partially preventing the transmission of vibrations originating from within the system itself, such as from transporting fluid through the flow cell from a pump or other vibration generating component. In one embodiment, the vibration damping component is designed to reduce the transmission of vibrations having a fundamental frequency of 60 Hz or greater to less than 1% of the initial amplitude. In one embodiment, the vibration damping component comprises a damping spring mechanism, at least two mass dampers, or any combination thereof.

[0016] In one embodiment, the controller is an active cooling component capable of controlling the temperature of the flow cell, the light source, the beam shaping optics, the optical detector array, or any combination thereof. In one embodiment, the active cooling component is in thermal communication with the flow cell, the light source, the beam shaping optics, the optical bench, the optical detector array, or any combination thereof via a heat transfer link. In one embodiment, the active cooling component comprises a thermoelectric cooler. In one embodiment, the thermoelectric cooler is provided in thermal communication with no external enclosure of the system. In one embodiment, the thermoelectric cooler is provided in thermal communication with a heat exchange structure for removing heat from the thermoelectric cooler and injecting heat into an environment external to the system. In one embodiment, the heat exchange structure is a finned heat exchanger. In one embodiment, the thermoelectric cooler is purged with a dry gas to prevent moisture condensation on the cold side. In one embodiment, the thermoelectric cooler is purged with a dry gas flowing across the hot side heat exchanger to enhance heat dissipation.

[0017] In one embodiment, the flow cell, light source, beam shaping optics, optical detector array, or any combination thereof, are configured to provide passive isolation to compensate for changes in system parameters in response to ambient conditions, internal stimuli, and / or external stimuli. In one embodiment, passive isolation is provided by one or more of the following features: incorporation of one or more vibration isolators, incorporation of one or more adhesive layers on the lens, incorporation of one or more thermosetting or thermoplastic mechanical restraints, reduction in size and / or mass of the light source and components, incorporation of a lens mount with a natural frequency of 150 Hz or greater, incorporation of a flow cell that is mechanically isolated from the light source and components, thermal expansion coefficient matching materials, and low thermal expansion coefficient optics.

[0018] In one embodiment, the light source provides a coherent incident beam, such as a Gaussian incident beam, to the flow cell. The systems and methods of the present invention are also well suited for structured beam interference detection, including dark beam interference detection. In one embodiment, the light source comprises one or more shaping and / or combining optical elements to generate one or more beams of electromagnetic radiation. In one embodiment, the one or more shaping and / or combining optical elements are diffractive elements, polarizing elements, intensity modulating elements, phase modulating elements, or any combination thereof. In one embodiment, the one or more beams of electromagnetic radiation comprise a structured non-Gaussian beam. In one embodiment, the one or more beams of electromagnetic radiation comprise a dark beam. In one embodiment, the one or more beams of electromagnetic radiation comprise a beam characterized by one or more line singularities. In one embodiment, the one or more beams of electromagnetic radiation comprise an anamorphic beam. In one embodiment, the one or more beams of electromagnetic radiation comprise a top hat anamorphic beam.

[0019] The system and method are compatible with a wide range of detectors and detector configurations. In one embodiment, a forward-facing on-axis detector pair is provided with scattering angles in the range of, for example, 0 degrees to 20 degrees. Differential detection can be used in the present system and method to provide a significant reduction in noise.

[0020] The systems and methods of the present invention provide for interference detection of particles, including detection, counting, and sizing of single particles in a fluid stream, and / or optical detection of particles having size dimensions of 100 nm or less in a flowing fluid. In one embodiment, the fluid is a liquid or a gas. In one embodiment, the system is for detecting particles in liquid chemicals. In one embodiment, the system is for detecting particles in ultrapure water. In one embodiment, the system is for detecting particles in high pressure gases. In one embodiment, the system is for detecting particles in air. In one embodiment, the system is for detecting particles on a surface.

[0021]

[0021] In one aspect, a method for detecting particles in a fluid includes providing a flow of fluid containing the particles; generating one or more beams of electromagnetic radiation using a light source, such as one or more coherent beams of electromagnetic radiation, generating electromagnetic radiation that is scattered by the particles by passing the one or more beams of electromagnetic radiation through a flow cell using beam shaping optics; and directing electromagnetic radiation from the flow cell to the optical detector array using at least one optical detector array in optical communication with the flow cell to enable interferometric detection of particles and / or optical detection of particles, at least one and optionally all having size dimensions of 100 nm or less, wherein the flow cell, light source, beam shaping optics, optical detector array, or any combination thereof are configured and / or controlled to maintain a high signal-to-noise ratio during the detection of the particles. In some embodiments, for example, the flow cell, the light source, the beam shaping optics, the optical detector array, or any combination thereof, are configured such that one or more particle detection system parameters are independently maintained to maintain a high signal-to-noise ratio and / or to avoid significant performance degradation during particle detection, such as during interference detection of particles and / or during optical detection of particles having size dimensions of 100 nm or less, where such particle detection system parameters may include one or more of the optical beam path, the position and / or alignment of the light source, the position and / or alignment of the beam shaping system, the position and / or alignment of the flow cell, the position and / or alignment of the beam collection system, the position and / or alignment of the detector, or any combination thereof.

[0022] In one embodiment of the method, an optical detector array is disposed in optical communication with the flow cell to receive incident electromagnetic radiation transmitted through the flow cell and electromagnetic radiation scattered by the particles, for example, where the electromagnetic radiation scattered by the particles includes forward scattered electromagnetic radiation. In one embodiment of the method, the incident electromagnetic radiation transmitted through the flow cell and the electromagnetic radiation scattered by the particles undergo constructive and / or destructive optical interference. In one embodiment of the method, the optical detector array is disposed at a scattering angle in the range of 0 degrees to 5 degrees relative to the optical axis of the incident beam, optionally in some applications at a scattering angle in the range of 0 degrees to 1 degree relative to the optical axis of the incident beam, optionally in some applications at a scattering angle in the range of 0 degrees to 0.5 degrees relative to the optical axis of the incident beam, optionally in some applications at a scattering angle in the range of 0 degrees to 0.1 degrees relative to the optical axis of the incident beam. In one embodiment of the method, the optical detector array is disposed in optical communication with the flow cell to detect interactions of the particles and the electromagnetic radiation scattered by the particles with the illuminating wavefront. In one embodiment, an optical detector array is provided for differential detection.

[0023]

[0023] In one aspect, a particle detection system includes a flow cell for flowing a fluid containing particles, a light source for generating one or more beams of electromagnetic radiation, such as one or more coherent beams of electromagnetic radiation including structured non-Gaussian beams, beam shaping optics for generating electromagnetic radiation that is scattered by the particles by passing the one or more beams of electromagnetic radiation through the flow cell, and at least one optical detector array for receiving the electromagnetic radiation from the flow cell, the optical detector array being oriented at an angle between 0 degrees and 0.and at least one optical detector array, the optical detector array being configured to provide a scattering angle within a range of 5 degrees, a light source being disposed in optical communication with the flow cell to receive incident electromagnetic radiation transmitted through the flow cell and electromagnetic radiation scattered by the particle, the beam shaping optics and the optical detector array being configured to enable structured beam interference detection, the system being configured such that at least one of temperature, pressure, degree of vibration, and degree of sonication, or any combination thereof, are each independently maintained within a selected tolerance range to maintain a high signal to noise ratio during detection of the particle, the system further comprising a controller operatively connected to the flow cell, the light source, the beam shaping optics, the optical detector array, or any combination thereof, such as an optical bench comprising the flow cell, the beam shaping optics, the optical detector array, or any combination thereof, the controller being for compensating for changes in the system parameters in response to ambient conditions, internal stimuli, external stimuli, or any combination thereof, and the controller optionally being configured to (i) adjust the at least one of temperature, pressure, degree of vibration, and degree of sonication, or any combination thereof, to maintain a high signal to noise ratio during detection of the particle. (ii) a beam alignment system, such as orthogonal optical sensors and one or more piezoelectrically actuated nanopositioners positioned in the system, for monitoring the position of the multiple beams and actively controlling the positioning and / or alignment of the flow cell, the light source, the beam shaping optics, the optical detector array, or any combination thereof; (ii) an isolator or isolators, such as vibration damping components, capable of at least partially preventing the transmission of vibrations from the external operating environment to the system, or at least partially preventing the transmission of vibrations originating from within the system itself, for isolating the flow cell, the light source, the beam shaping optics, the optical detector array from changes in ambient conditions, internal stimuli, external stimuli of the operating environment, or any combination thereof; and / or (iii) one or more active cooling components, such as thermoelectric coolers, capable of controlling the temperature of elements of the system, such as the flow cell, the light source, the beam shaping optics, the optical detector array, or any combination thereof; and optionally, the controller is configured for closed-loop feedback control.

[0024]

[0024] In one embodiment, a method for detecting particles in a fluid includes the steps of: (i) providing a flow of the fluid containing particles; (ii) generating one or more beams of electromagnetic radiation using a light source, the beams comprising a structured non-Gaussian beam; (iii) generating electromagnetic radiation that is scattered by the particles by passing the one or more beams of electromagnetic radiation using beam shaping optics through the flow cell; and (iv) directing the electromagnetic radiation from the flow cell to an optical detector array, the optical detector array being oriented at an angle between 0 degrees and 0.5 degrees relative to the optical axis of the incident beam or beams of electromagnetic radiation.and (b) optically detecting particles having a size dimension of 100 nm or less, wherein the flow cell, the light source, the beam shaping optics, the optical detector array, or any combination thereof, is configured and / or controlled to maintain a high signal to noise ratio during said detection of said particles, the method further comprising providing a controller operatively connected to an optical bench or the like comprising the flow cell, the light source, the beam shaping optics, the optical detector array, or any combination thereof, the controller being for compensating for changes in the system parameters in response to ambient conditions, internal stimuli, external stimuli, or any combination thereof, the controller optionally being configured and / or controlled to (i) position the one or more beams of electromagnetic radiation to maintain a high signal to noise ratio during said detection of said particles. (ii) a beam alignment system, such as an orthogonal optical sensor and one or more piezoelectrically actuated nanopositioners positioned in the system, for monitoring and actively controlling the positioning and / or alignment of the flow cell, the light source, the beam shaping optics, the optical detector array, or any combination thereof; (ii) an isolator or isolators, such as vibration damping components, capable of at least partially preventing the transmission of vibrations from the external operating environment to the system, or at least partially preventing the transmission of vibrations originating from within the system itself, for isolating the flow cell, the light source, the beam shaping optics, the optical detector array from changes in ambient conditions, internal stimuli, external stimuli of the operating environment, or any combination thereof; and / or (iii) one or more active cooling components, such as thermoelectric coolers, capable of controlling the temperature of elements of the system, such as the flow cell, the light source, the beam shaping optics, the optical detector array, or any combination thereof; and optionally, the controller is configured for closed-loop feedback control.

[0025]

[0025] While not wishing to be bound by a particular theory, there may be discussion herein of a belief or understanding of the underlying principles related to the systems, devices, and methods disclosed herein. It is recognized that regardless of the ultimate correctness of a mechanistic explanation or hypothesis, embodiments of the invention may nevertheless be effective and useful. [Brief description of the drawings]

[0026] [Figure 1A] FIG. 1 provides a schematic diagram of a system for interferometric detection of particles in a fluid flow with vibration isolation of the optical bench, showing a single pass optical geometry. [Figure 1B] FIG. 1 provides a schematic diagram of a system for interferometric detection of particles in a fluid flow with vibration isolation of the optical bench, showing a dual-path optical geometry. [Figure 1C] FIG. 2 is a schematic diagram of an optical particle counter housing component for providing vibration isolation of system components including an optical bench and components supported by the optical bench. [Diagram 2] 1 is a plot of transmissibility versus frequency for an example vibration isolator. [Figure 3A] FIG. 1 is a schematic diagram illustrating an on-board alignment control system that uses orthogonal optical sensors and a piezoelectrically actuated fast steering mirror (FSM) for closed-loop control of optical alignment. [Figure 3B] FIG. 1 is a schematic diagram illustrating an on-board alignment control system that uses orthogonal optical sensors and a piezoelectrically actuated fast steering mirror (FSM) for closed-loop control of optical alignment. [Figure 3C] FIG. 13 is a schematic diagram showing example intensity patterns illustrating the system in a stable aligned configuration. [Figure 3D] FIG. 13 is a schematic diagram showing example intensity patterns illustrating the system in an unstable misaligned configuration. [Figure 4]FIG. 1 is a flow diagram showing a series of steps and criteria for closed-loop feedback control of optical alignment using a quad detector signal and a fast steering mirror (FSM) as inputs to provide controlled optical alignment. [Diagram 5] 1 is a graph of temperature change versus length change over a region of interest (eg, the length and width of an optical bench). [Figure 6] FIG. 1 is a schematic diagram of a system for detection of particles in a fluid flow with a temperature control system. [Figure 7] 1 is a schematic diagram illustrating an example approach for vibration isolation and cooling in a liquid particle counter system. [Figure 8] FIG. 2 is a schematic perspective view of a liquid particle counter system showing elements for providing vibration isolation and temperature control. [Figure 9A] FIG. 9 is a schematic perspective view of a liquid particle counter system complementary to the liquid particle counter system of FIG. 8. [Figure 9B] FIG. 2 is an expanded schematic diagram of the liquid particle counter system showing the components of the vibration isolator and how it is coupled to the optical bench. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0027]

[0039] In the following description, numerous specific details of the devices, device components, and methods of the present invention are set forth in order to provide a thorough explanation of the precise nature of the invention. However, it will be apparent to one skilled in the art that the present invention may be practiced without these specific details.

[0028]

[0040] Generally, the terms and phrases used herein have their art-recognized meanings that can be found by reference to standard texts, periodical literature, 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.

[0029]

[0041] "Particle" refers to a small object that is often considered a contaminant. A particle may be any material that is formed by the action of friction, for example, when two surfaces are in mechanical contact and there is mechanical movement. A particle may consist of an aggregate of materials such as dust, dirt, smoke, ash, water, soot, metals, oxides, ceramics, 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, and other single-celled microorganisms. In some embodiments, for example, biological particles are characterized by a size dimension (e.g., effective diameter) in the range of 0.1-15 μm, optionally in some applications in the range of 0.5-5 μm.

[0030]

[0042] Particles may refer to small objects that absorb, emit, or scatter light, and thus are detectable by optical particle counters. As used herein, "particles" is intended to exclude individual atoms or molecules of a carrier fluid or sample medium, such as water, air, process liquid chemicals, process gases, etc. In some embodiments, the particles are initially present on a surface, such as a tool surface in a microfabrication facility or a production surface in a pharmaceutical manufacturing facility, and are then dislodged from the surface and analyzed in the liquid. Some systems and methods can detect particles that comprise a size dimension and, optionally, an aggregate of material having all size dimensions, such as an average or effective diameter, average or effective length, and / or average or effective width greater than 5 nm, 10 nm, 20 nm, 30 nm, 50 nm, 100 nm, 500 nm, 1 μm or greater, or 10 μm or greater. Some embodiments of the present invention are capable of detecting particles having a size dimension, and optionally all size dimensions such as an average or effective diameter, an average or effective length, and / or an average or effective width, selected from the ranges of 10 nm to 150 μm, optionally in some applications 10 nm to 10 μm, optionally in some applications 10 nm to 1 μm, optionally in some applications 10 nm to 0.5 μm, and optionally in some applications 10 nm to 250 μm.

[0031]

[0043] The phrase "detecting a particle" broadly refers to sensing the presence of, identifying, counting, and / or characterizing a particle, such as characterizing a particle with respect to a size dimension, such as an average or effective diameter, an average or effective length, and / or an average or effective width. In some embodiments, detecting a particle refers to counting the particles. In some embodiments, detecting a particle refers to counting particles that correspond to a size characteristic or a range of size characteristics (e.g., a size bin), such as counting particles that correspond to one or more ranges of an average or effective diameter, an average or effective length, and / or an average or effective width. In some embodiments, detecting a particle refers to characterizing and / or measuring a physical property of a particle, such as a cross-sectional dimension, an average or effective diameter, an average or effective length, an average or effective width, a shape, aerodynamic size, or any combination thereof. In some embodiments, particle detection is performed in a flowing fluid, such as a gas, having a volumetric flow rate selected over the range of 0.05 CFM to 10 CFM, optionally for some applications 0.1 CFM to 5 CFM, optionally for some applications 0.5 CFM to 2 CFM. In some embodiments, particle detection is performed in a flowing fluid, such as a liquid, having a volumetric flow rate selected over the range of 1 to 1000 mL / min.

[0032]

[0044] "Optical particle counter" or "particle counter" are used interchangeably and refer to a particle detection system that uses optical analysis and / or detection to detect, count, and / or characterize particles, e.g., by analyzing particles in a fluid stream and / or in a fluid sample. Optical particle counters include liquid particle counters and aerosol particle counters, including systems that can detect individual single particles in a fluid stream, e.g., a liquid or gas stream, and characterize the number of particles per volume of analyzed fluid based on, e.g., a size criterion or a range of size criteria, e.g., average or effective diameter, average or effective length, and / or average or effective width (e.g., one or more size bins).

[0033]

[0045] In some embodiments, an optical particle counter delivers a beam of electromagnetic radiation (e.g., via a laser or light emitting diode) to an interaction region, such as an analysis region of a flow cell, where the beam interacts with particles in the fluid stream. Illumination may involve focusing, filtering, and / or shaping (e.g., stretching) the incident beam delivered to the interaction region. Detection and / or characterization of the particles may be achieved by detection and analysis of electromagnetic radiation scattered, emitted, and / or transmitted from the interaction region. Detection may involve focusing, filtering, and / or shaping the electromagnetic radiation scattered, absorbed, concealed, and / or emitted by the particles onto one or more photodetectors, such as an optical detector array. Various detectors for optical particle counters are known in the art including, for example, single detection elements (e.g., photodiodes, photomultiplier tubes, etc.), optical detector arrays (e.g., photodiode arrays, CMOS detectors, active pixel sensors (APS), charge-coupled devices (CCDs), metal oxide semiconductor (MOS) detectors, etc.), cameras, and can be implemented using various detector orientations known in the art. Optical particle counters can incorporate differential detection including split beam differential detection. Optical particle counters can include condensation particle counters, condensation nuclei counters, etc. When used in the context of a condensation particle counter, an optical particle counter portion refers to a detection system (e.g., electromagnetic radiation source, optics, filters, optical collection, detector, processor, etc.) for characterizing particles that have undergone nucleation and / or growth upstream.

[0034]

[0046] In one embodiment, for example, an optical particle counter comprises a light source for generating a beam of electromagnetic radiation, beam steering and / or shaping optics for directing and focusing the beam onto a region where a fluid sample is flowing, e.g., a region where a liquid or gas is flowing through a flow cell. A typical optical particle counter comprises a photodetector, such as an optical detector array, in optical communication with the flow cell, and collection optics for collecting, shaping, and / or imaging electromagnetic radiation scattered, transmitted, and / or emitted by particles passing through the incident beam. The particle counter may further comprise electronics and / or processors (e.g., implemented by firmware and / or software) for readout, signal processing, and / or analysis of electrical signals generated by the photodetector, including current-to-voltage converters, pulse height analyzers, signal filtering electronics, amplification electronics, and the like. The optical particle counter may also comprise one or more fluid actuation systems, such as pumps, fans, blowers, and the like, for generating a fluid flow for transporting the particle-containing fluid sample through an analysis region of the flow cell, e.g., for generating measurements characterized by volumetric flow rate. In some embodiments, the optical particle counter includes a fluid actuation system for generating a selected flow rate, such as a selected flow rate over a range of 0.05 CFM to 10 CFM, optionally in some applications 0.1 CFM to 5 CFM, optionally in some applications 0.5 CFM to 2 CFM. In some optical particle counters, flow rates are generated for a sample comprising one or more liquids including selected flow rates over a range of 1 to 1000 mL / min.

[0035]

[0047] The phrase "interferometric detection of particles" refers to systems and methods that use at least a component of optical interference to detect, count, and / or characterize one or more particles. In some embodiments, coherent beams of electromagnetic radiation are superimposed or otherwise combined to cause optical interference to sense, count, and / or determine size characteristics of particles that interact with at least a portion of the electromagnetic radiation. "Structured beam interferometric detection" refers to interferometric measurement systems and methods in which a structured probe beam of electromagnetic radiation having a non-Gaussian intensity distribution is passed through a flow cell containing particles, and light (e.g., transmitted light, scattered light (e.g., forward scattered light), etc.) from the flow cell is detected using an optical detector array to sense, count, and / or characterize the particles. "Heterodyne interferometric detection" refers to interferometric systems and methods in which a probe beam of coherent electromagnetic radiation is passed through a flow cell and combined with a separate reference beam, and the combination of the probe beam and the reference beam is detected using an optical detector array to sense, count, and / or characterize the particles. In some embodiments, the particle counter is configured to perform heterodyne interferometric detection of said particles by collecting off-axis scattered light and combining the off-axis scattered light with a reference beam to generate an interference signal.

[0036]

[0048] A high signal-to-noise ratio (S / N) is required to detect and count small particles (e.g., less than 100 nm effective diameter) in clean and ultra-clean fluids in a manner that provides statistically significant data. A high S / N ratio allows clear detection of nanoparticles above the noise floor. As used herein, "statistically significant data" refers to the detection of enough particles per unit time so that the contamination level in the fluid can be accurately assessed. In some embodiments, a high S / N does not necessarily relate directly to sizing accuracy. For example, in some optical particle counters, the beam waist occupies a small portion of the flow cell channel, so the approach monitors a subset of the entire flow so that particles can pass through the edges of the beam where the irradiance is less than in the center. If a 50 nm particle passes through the outer edge of the beam, it may generate a similar signal as a 10 nm particle passing through the center of the beam. Thus, some optical particle counters may have a high S / N and be able to detect 2 nm particles, although the sizing accuracy is not very high. For some current optical particle counters and methods, the goal is to be able to count enough particles to make a quantitative, statistically sound assessment of the contamination level of an ultrapure fluid in the shortest possible time. For example, current state-of-the-art particle counters may take up to 40 minutes to count enough particles to give a statistically relevant concentration (acceptable relative standard deviation) measurement when monitoring a state-of-the-art ultrapure water system. By improving and maintaining a high S / N through current systems and methods, the time interval required to measure this statistically acceptable minimum particle count can be reduced by a factor of 10 or more. This provides value by allowing users to more quickly identify deviations from process control limits.

[0037]

[0049] The phrase "high signal-to-noise ratio" refers to a signal-to-noise ratio of an optical particle detection system that is sufficient for accurate and sensitive detection of particles in a fluid stream, including particles characterized by small physical dimensions (e.g., effective diameters of 200 nm or less, optionally in some embodiments 100 nm or less, and optionally in some embodiments 50 nm or less). In one embodiment, "high signal-to-noise ratio" refers to a signal-to-noise ratio that is high enough to sense particles characterized by small physical dimensions, such as particles having effective diameters of up to 20 nm, optionally in some embodiments 10 nm or less, and optionally in some embodiments 1 nm or less. In one embodiment, "high signal-to-noise ratio" refers to a signal-to-noise ratio that is high enough to accurately detect and count particles with a false positive rate of 50 counts / L or less, for example, for detection of particles with effective diameters selected over the range of 1-1000 nm. In one embodiment, "high signal-to-noise ratio" refers to a signal-to-noise ratio that is high enough to perform a minimum statistically acceptable particle count in a time frame that is at least 10 times shorter than conventional optical particle counters.

[0038]

[0050] The phrase "significantly degraded performance of the particle counting process" refers to a degradation in the ability of the particle detection system to detect and count particles in a flowing fluid. In some embodiments, significant degradation of the particle counting process refers to a shift in the detection threshold voltage in the smallest size channel by 20% or more. In some embodiments, significant degradation of the particle counting process refers to an increase in the false count rate of 50 counts / L or more. In some embodiments, significant degradation of the particle counting process refers to an increase in the time required to perform the smallest statistically acceptable particle count by 5 times or more, optionally in some embodiments by 10 times or more. In some embodiments, significant degradation of the particle counting process, for example as a result of poorly controlled noise sources, refers to a degradation in S / N, thereby resulting in poor detectability of the smallest particles. For example, a degradation in S / N causes a detection signal from a 50 nm particle to look like a signal from a 20 nm particle, and the 20 nm particle signal becomes indistinguishable from noise, resulting in reduced detectability, fewer particles being counted per unit time, and / or false counts due to increased noise levels.

[0039]

[0051] The term "differential detection" refers to techniques and systems that use differential signals from a forward-facing on-axis detector pair, for example, at scattering angles in the range of 0 degrees to 0.5 degrees relative to the optical axis of the incident beam, and optionally in some applications at scattering angles in the range of 0 degrees to 0.1 degrees relative to the optical axis of the incident beam, and optionally at or near 0 degrees. A single pixel pair for differential detection can be formed using a minimum of two pixels to generate a differential signal (e.g., one on the top (or top) and one on the bottom (or bottom)). Alternatively, multiple pixel pairs can be used, for example, by using multiple pixels for each active detector area (e.g., top and bottom active areas) of a differential detector, such as a segmented differential detector with one or more pixel pairs, where one pixel of each pixel pair corresponds to the top active detector area and the other pixel of each pixel pair corresponds to the bottom active area. The number of pixel pairs can range, for example, from 1 to 500 pixels, and in some applications may range from 50 to 100 pixels. In some embodiments, a differential signal is generated by differentially adding signals from pairs of pixels corresponding to different active areas of a segmented detector array, such as the top and bottom halves. Differential detection can be used in the present systems and methods to reduce noise and therefore improve the signal-to-noise ratio. In some embodiments, for example, differential detection is used to detect a combination of incident electromagnetic radiation transmitted through the flow cell and electromagnetic radiation forward scattered by one or more particles in the fluid flow in the flow cell. In some embodiments, for example, the distribution of incident light has a power distribution that is matched between the first and second active detection areas (e.g., the top and bottom halves) of the differential detector, such that, for example, the first and second active detection areas are characterized by incident radiation powers within 10%, optionally within 5%, and optionally in some applications within 1%. Differential detection includes techniques and systems with closed-loop control, for example, based on an evaluation of the noise amplitude of the differential signal when no particles are present (i.e., when there is no scattering from particles).In some embodiments, a steering mirror is used to adjust the incident beam position on the detector to reduce or minimize the noise level of the differential signal that can occur when the beam power is split evenly between the first and second active detector elements (e.g., the upper and lower elements of the detector). Closed-loop control can also be achieved by translating the detector position and rotating the detector to align the beam axis with the detector axis to reduce or minimize the noise level of the differential signal.

[0040]

[0052] "Structured beam" refers to a coherent beam of electromagnetic radiation (e.g., laser) having a non-Gaussian spatial intensity distribution. Structured beams include beams characterized by attenuated regions such as dark beams, beams with line focuses with dark line singularities, beams characterized by two or more discrete intensity lobes, and the like. In one embodiment, a structured beam corresponds to a transverse mode such as TEM01. Structured beams include focused beams, composite beams, and laser beams. Structured and dark beams can be generated by techniques known in the art, including the use of optical masks, modification of laser cavities, combining multiple beams, spatial and / or polarizing filters, and other manipulations such as interference or polarization modification schemes.

[0041]

[0053] "Structured beam detection" refers to systems and methods in which a structured beam of electromagnetic radiation having a non-Gaussian intensity distribution is passed through a flow cell containing particles, and light (e.g., transmitted light, scattered light (e.g., forward scattered light, etc.)) from the flow cell is detected using an optical detector array to sense, count, and / or characterize the particles.

[0042]

[0054] "Dark beam detection" refers to systems and methods in which a dark beam of electromagnetic radiation having a spatial intensity profile with regions of attenuated intensity, e.g., a centerline decrease in intensity, is passed through a flow cell containing particles and detected using an optical detector array to sense, count, and / or characterize the particles.

[0043]

[0055] "Beam propagation axis" refers to the axis parallel to the direction of travel of a beam of electromagnetic radiation.

[0044]

[0056] "Optical communication" refers to components arranged in a manner that allows light to be transmitted between the components. Optical communication includes two elements in direct optical communication, where light travels directly between the elements, and two elements in indirect optical communication, where light travels between the elements via one or more additional optical elements, such as one or more lenses, mirrors, windows, beam splitters, optical fibers, phase masks, wave plates, beam combiners, optical filters, etc., or any combination thereof.

[0045]

[0057] "Optical axis" refers to the direction that electromagnetic radiation propagates through a system.

[0046]

[0058] "Optical detector array" refers to an optical detector that can spatially resolve an input signal (e.g., electromagnetic radiation) in two dimensions across the active area of ​​the detector. The optical detector array can generate an image, e.g., an image corresponding to an intensity pattern on the active area of ​​the detector. In one embodiment, the optical detector array comprises an array of individual detector elements, also referred to herein as pixels, such as a two-dimensional array of photodetectors, charge-coupled device (CCD) detectors, complementary metal-oxide semiconductor (CMOS) detectors, metal-oxide semiconductor (MOS) detectors, active pixel sensors, microchannel plate detectors, or a two-dimensional array of photodiodes.

[0047]

[0059] A "light source" refers to a device or device component for generating and / or delivering electromagnetic radiation to a sample. The term is not limited to visible light, such as visible light, but is used broadly to include any electromagnetic radiation, including visible light, ultraviolet radiation, and / or infrared radiation. The light source can 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, to name a few examples. In some embodiments, the light source is for generating one or more beams of electromagnetic radiation, such as one or more coherent beams of electromagnetic radiation, for example, to generate a probe beam in an optical particle counter. In an embodiment, the light source can include one or more components, such as a beam shaping system, a phase mask, a beam combiner, a polarization controller, a wave plate, or other components for generating a structured beam, such as a dark beam, to provide a probe beam in an optical particle counter.

[0048]

[0060] In some embodiments, the beam shaping optics is in optical communication with the light source to receive electromagnetic radiation from the light source, the beam shaping optics configured to provide one or more beams of electromagnetic radiation, e.g., one or more beams having selected intensity, directional and / or spatial characteristics, to the flow cell. The beam shaping optics in certain embodiments may comprise one or more optical elements for focusing, expanding, steering, directing and / or combining light received from the light source. The beam shaping optics in certain embodiments may comprise one or more lenses, reflectors, filters, expanders, polarization controllers, beam combiners, wave plates, prisms, phase masks, apertures, modulators, actuators, or any combination thereof. The beam shaping optics in certain embodiments is arranged and configured to provide a focused beam of electromagnetic radiation to the flow cell. The beam shaping optics in certain embodiments is configured to provide a high aspect ratio beam to the flow cell, such as a beam characterized by an aspect ratio selected from the range of 10:1 to 200:1.

[0049]

[0061] The terms "electromagnetic radiation" and "light" are used synonymously in this description 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 thereof having wavelengths from about 100 nanometers to about 15 microns.

[0050]

[0062] A "high aspect ratio" beam refers to a light beam, such as a laser beam, including a structured beam or a dark beam, having an aspect ratio selected from the range of 10:1 to 200:1.

[0051]

[0063] "Optical detection of particles having a size dimension of 100 nm or less" refers to systems and methods capable of detecting particles having size dimensions, such as effective or average diameter, effective or average length, effective or average width, at least one, and optionally all, of 100 nanometers or less. In some embodiments, "optical detection of particles having a size dimension of 100 nm or less" refers to systems and methods capable of counting particles having at least one, and optionally all, of 100 nm or less in a fluid flow as a function of, for example, time, flow rate, etc. In some embodiments, "optical detection of particles having particles with at least one, and optionally all, size dimensions of 100 nm or less" refers to systems and methods that can characterize particles in a fluid stream based on size attributes, effective or average diameter, effective or average length, effective or average width, etc., by classifying the particles as corresponding to a size range (or size bin), such as size ranges corresponding to 100 nm or less, 90 nm or less, 80 nm or less, 70 nm or less, 60 nm or less, 50 nm or less, 40 nm or less, 30 nm or less, 20 nm or less, 10 nm or less, 5 nm or less, 1 nm-10 nm, 10 nm-20 nm, 20 nm-30 nm, 30 nm-40 nm, 40 nm-50 nm, 50 nm-60 nm, 60 nm-70 nm, 70 nm-80 nm, 80 nm-90 nm, 90 nm-100 nm, or any combination of these ranges. In some embodiments, "optical detection of particles having a size dimension of 100 nm or less" refers to systems and methods that can detect particles having size dimensions such as effective or average diameter, effective or average length, effective or average width, at least one and optionally all of which are greater than 100 nm, in addition to detecting particles of 100 nm or less. Examples of methods and systems for detecting particles of 100 nm or less include, but are not limited to, light scattering-based methods and systems, fluorescence-based methods and systems, light quenching-based methods and systems, interference-based methods and systems, condensation nucleus counting-based methods and systems, and any combination thereof.

[0052]

[0064] The systems and methods incorporate active and / or passive components to prevent, mitigate and / or compensate for the effects of internal or external stimuli and / or changes in operating conditions that may adversely affect particle detection using interferometric means and / or optical detection of particles having size dimensions of 100 nm or less. Features of the systems and methods include controllers, compensators and / or isolators that enhance the optical alignment and / or stability of the particle detection system during interferometric detection of particles and / or optical detection of particles having size dimensions of 100 nm or less. In some embodiments, the particle detection system has a "particle counter box in a box" geometry with vibration, acoustic and / or thermal control to minimize changes in optical alignment during interferometric detection of particles and / or optical detection of particles having size dimensions of 100 nm or less. In one embodiment, for example, the "optical bench" or components thereof are physically, acoustically and / or thermally isolated from external environmental inputs by an enclosure. In one embodiment, for example, an interfering particle detection system incorporates an isolator, such as a mesh isolator, to provide vibration stability, for example, by actively compensating for external or internal vibration sources.

[0053]

[0065] In one embodiment, for example, the particle detection system includes one or more passive or active components that improve vibration tolerance rather than reduce vibration, such as by incorporating one or more of the following features or aspects: (i) incorporating lenses and other optical components using epoxy; (ii) reducing size / mass; (ii) maintaining the lens mount at or near its natural frequency of above 150 Hz; (iii) implementing techniques to design the optical mount and mounted optics; (iv) using optics / lasers that are thermally and vibrationally isolated from the housing; and / or (v) using a flow cell that is mechanically isolated from the optics.

[0054]

[0066] The present invention can be further understood by the following non-limiting examples.

[0055]

[0067] Example 1: Interference detection with vibration isolation

[0068] One of the important causes of performance degradation in optical systems is vibration imposed either from the environment or inherent to the optical system. These inputs can be either periodic or random, with both frequency and amplitude components. Cooling fans, active mechanisms, and general industrial environments can contribute to vibration sources and have frequency components. More specifically, industrial environments tend to have a first spectral peak in the input at about 60 Hz, with decreasing amplitude at harmonics. It is this first spectral peak that most commonly causes degradation in the performance of optical systems, for example optical particle counting. Symptoms of performance degradation can be both image blurring from in-plane and defocusing from out-of-plane motion. Loss of aim due to optical component displacement can be a major performance impact occurring with vibration excitation if the natural frequency of the component mount falls into one of the harmonics.

[0056]

[0069] In certain embodiments, methods and components are used in particle detection systems to prevent performance degradation due to, for example, internal and environmental vibrations. The design of the system in some embodiments is based on isolating the optical system from the external environment. For example, in a "box-within-a-box" design, the optical assembly is mounted in an isolator that prevents transmission of external environmental vibration sources with frequency content above the first fundamental mode of 60 Hz. Within the optical assembly, some or all of the mounts are designed to have natural frequencies well above the fundamental modes of most vibration sources.

[0057]

[0070] Another cause of performance degradation in optical assemblies is movement of optical components within the mount, either due to vibration inputs or thermal effects. In some embodiments, to reduce the impact of these effects, some or all of the optical components are constrained to the mount by adhesives to prevent stick-slip motion that may be induced by vibration sources or thermal effects. Additionally, the use of fans to control temperature is decoupled from the optical assembly to effectively eliminate that vibration source.

[0058]

[0071] A secondary source of vibration input is the coupling of external excitation from an external source to the optical assembly. These sources can be due to fluid flow in the test cell, electrical cables, or connections required to pass from the external environment to the optical assembly. To isolate these sources, flexible links are installed between the external containment and the optical assembly. The flexible links act as isolators since their ability to transmit vibrations is reduced or eliminated. Thus, these isolated links do not degrade the performance of the optical system.

[0059]

[0072] Vibration levels can be linked to system performance to establish general limits based on the sensitivity of the particle measurement system, for example, as the feature size of interest decreases, the tolerable level of vibration applied to the measurement tool also decreases.

[0060]

[0073] Contrast this with general environmental vibration inputs (from all external sources) and the need to isolate the particle measurement system from external sources becomes apparent.

[0061]

[0074] Figure 1A provides a schematic diagram of an interferometric detection system for particles in a fluid flow with vibration isolation of an optical bench. As shown in Figure 1A, the particle detection system (200) includes a flow cell (210) for transporting a flow of fluid (150) containing particles (schematically shown as a circle within the flow cell (210)), such as a particle-bearing gas or liquid stream. A light source (220), such as a laser source, generates electromagnetic radiation that is fed into a beam steering and / or shaping system (221) for generating a probe beam (222), such as a structured beam, such as a dark beam, that is fed into the flow cell (210). Light from the flow cell 210, including the port of the probe beam passing through the flow cell (210), and light scattered (e.g., forward scattered) or emitted from the flow cell (210) is provided to an on-axis optical detector array (240), such as a segmented 1D or 2D optical detector (240A and 240B) comprising one or more pixel pairs in operative communication with a processor (101), such as a firmware or software implemented processor, to provide an output signal to the processor (101). The optical detector array (240) and / or the processor (101) may perform differential detection, for example, in a configuration where each individual segmented detector area is located on a different intensity lobe of a structured beam, such as a dark beam. Optionally, collection and / or shaping optics (223) are provided between the flow cell 210 and the detector 240 to collect, shape and / or filter the light from the flow cell 210.

[0062]

[0075] One or more vibration isolators (205) are provided to actively or passively isolate the light source (220), beam steering and shaping system (221), flow cell (210), optical detector array (240), collection and / or shaping optics (223), and / or any combination of these components from internal or external vibration sources. The incorporation of vibration isolators (205) may also be used in conjunction with particle detection systems that employ heterodyne interferometric and / or optical detection of particles having dimensions of 100 nm or less.

[0063]

[0076] The processor (101) receives and analyzes output signals from the optical detector array (240), e.g., via generation and analysis of differential signal combination (e.g., differential addition, subtraction, etc.) of signals from the segmented 1D or 2D optical detectors (240A and 240B), for detection of particles, e.g., by counting and / or size characterization as a function of the analyzed sample volume and / or time. In some embodiments, for example, the optical detector array (240) is positioned at a scattering angle in the range of 0 degrees to 5 degrees relative to the optical axis of the incident beam, optionally at a scattering angle in the range of 0 degrees to 0.5 degrees relative to the optical axis of the incident beam, and optionally at a scattering angle in the range of 0 degrees to 0.1 degrees relative to the optical axis of the incident beam.

[0064]

[0077] Also shown in FIG. 1A is an optional side scatter detector (268) and side scatter collection optics (267) positioned off-axis relative to the beam propagation axis of the probe beam (222) and the detector axis of the optical detector array (240). The side scatter collection optics (267), such as one or more lenses and / or mirrors, are positioned to receive off-axis scattered light resulting from interactions with the particles and the probe beam in the flow cell (210). The side scatter collection optics (267) directs, and optionally images, at least a portion of the collected scattered light to the side scatter detector (268) in operative communication therewith to provide an output signal to the processor (101) for analysis to detect and / or characterize the particles. Optionally, one or more vibration isolators (205) are provided to actively or passively isolate the scatter collection optics (267), the side scatter detector (268), and / or any combination thereof from internal or external vibration sources.

[0065]

[0078] FIG. 1B provides a schematic diagram of another system for interferometric detection of particles in a fluid flow with vibration isolation of the optical bench, where the optical geometry is configured to provide a dual-path optical geometry. As shown in FIG. 1B, the system (200) includes one or more vibration isolators (205) provided to actively or passively isolate the light source (220), the beam steering and shaping system (221), the flow cell (210), the beam splitter (265), the mirror (275), the optical detector array (240), or any combination thereof, from internal or external vibration sources. As shown in FIG. 1B, the beam splitter (265) and the mirror (275) are provided to provide a dual-path optical geometry. In the embodiment shown in FIG. 1B, the beam steering and shaping system (221) provides a high aspect ratio beam that is fed to the flow cell (210), and the optical detector array (240) is configured as a paired detector array. The depicted optical geometry allows for constructive and destructive interference of the beams which aids in sensitivity. The use of dual-path optical geometry and differential detection also aids in sensitivity. The use of a high aspect ratio beam increases the amount of sample in which particles can be detected, thereby increasing the amount of sample that can be monitored per unit time.

[0066]

[0079] Optionally, the beam steering and shaping system (221) provides a high aspect ratio beam, such as a beam characterized by an aspect ratio selected from the range of 10:1 to 200:1, provided to the flow cell (210), and the optical detector array (240) is configured as a paired detector array including paired detector arrays (240A and 240B, shown diagrammatically separately for clarity, extended from their positions within the detector (240) and next to example signals corresponding to particle detection events, below the particle detection schematic). The optical detector array (240) may be configured for differential detection, where the paired detector arrays (240A and 240B) are optionally positioned over an intensity lobe of a structured beam, such as a dark beam. In some embodiments, for example, the optical detector array is positioned at a scattering angle in the range of 0 degrees to 5 degrees relative to the optical axis of the incident beam, and optionally at a scattering angle in the range of 0 degrees to 0.5 degrees relative to the optical axis of the incident beam.

[0067]

[0080] 1B also shows representative signals from the optical detector array (240) as a function of time for a particle passing through the beam in the flow cell (or particle trajectory through the beam), where the solid line is the signal from detector array 240A and the dotted line is the signal from detector array 240B. As shown in FIG. 1B, the signals from each pair of detector arrays (240A and 240B) are each characterized by a minimum and a maximum value and are inverted with respect to each other. The signals from each pair of detector arrays (240A and 240B) may be combined, for example, via differential addition, subtraction, multiplication, etc., to provide a signal, such as a differential signal, that can be analyzed to provide precise information regarding the size, optical properties (e.g., refractive index) and composition of the particle.

[0068]

[0081] FIG. 1C provides a schematic diagram of the housing components of the optical particle counter for vibration isolation of the system components including the optical bench and the components supported by the optical bench. As shown in FIG. 1C, the housing (250) encloses the optical bench (255) and the system components supported by the optical bench, such as the light source, the beam steering and shaping system, the flow cell, the collection and / or shaping optics, the optical detector, the beam splitter, the phase mask, the optical alignment system, the actuator, the piezoelectric controller, the temperature controller, etc., or any combination of these components (Note: for clarity purposes, the optical components are not shown in FIG. 1B). A vibration isolator (260), such as a damper and / or a compensator, is provided in operative communication with the optical bench (255) such that the transmission of vibrations from external sources is minimized or avoided, e.g., to maintain a high signal-to-noise ratio to avoid degradation of the performance of the optical particle counter.

[0069]

[0082] In one embodiment, for example, the method used to isolate the internal measurement equipment from the external environment is to mount an "optical bench" on an isolator, several of which are commercially available. A common form of isolator is a damped spring mechanism designed to transmit only vibration inputs below its natural frequency. Vibration inputs above the natural frequency of the isolator are damped or reduced. The amount of amplitude reduction varies depending on the form of the isolator. For example, commercially available isolators are available that can reduce the transmitted vibrations up to 90% of their original amplitude when properly implemented in a design. Figure 2 provides a plot of transmissibility versus frequency for an example isolator. As shown in Figure 2, below about 8 Hz (the natural frequency of the isolator), the vibration input is transmitted through the isolator. In this example, the transmissibility is about 1 and increases up to the natural frequency of the isolator (note the peak at about 8 Hz). The amplitude of the transmitted vibration energy then decreases with frequency. As shown in Figure 2, it is less than 1% at 60 Hz, which is the first and typically largest input frequency.

[0070]

[0083] Example 2: Laser beam drift correction

[0084] Laser beam aiming can drift over time, which in turn can adversely affect the performance of interferometric particle detection systems that depend on a stable pointing direction.

[0071]

[0085] To address misalignment due to laser beam drift and other sources, a laser beam steering subsystem can be incorporated into the system using a piezo-actuated fast steering mirror (FSM) and a sensor that provides feedback for position error correction. A commonly used sensor is a quad-cell detector. The position (or position error) on the sensor can be calculated by comparing the levels of the signals on the active pixels. The error can be deconvolved into a coordinate position error. A second FSM is utilized some distance from the first FSM and coupled with a similar position sensor to provide angular error correction. The sensor provides position error signals that are subsequently used to effect changes in the position of the fast steering mirror. The position changes of the FSM correct the laser beam displacement and angular error.

[0072]

[0086] 3A and 3B provide schematic diagrams illustrating an implementation alignment control subsystem for closed-loop control of optical alignment. For example, a photodetector with an orthogonal photosensor may be configured to provide a signal that provides an input, and a piezo-actuated fast steering mirror (FSM) may be provided to provide an output for closed-loop control of the optical alignment.

[0073]

[0087] FIG. 3A provides a schematic diagram showing an optical beam path in an alignment control system comprising a light source, a first fast steering mirror (FSM), a first beam splitter, a first quad cell detector, a second fast steering mirror (FSM), a second beam splitter, and a second quad cell detector. As shown in FIG. 3A, the output from the laser light source is provided to the first fast steering mirror as an incident beam. A second portion of the beam is directed to the first beam splitter, which allows a portion of the beam to continue, splitting the portion of the beam to the quad cell detector. The portion of the beam that continues through the beam splitter is incident on the second fast steering mirror (FSM). The reflected beam is directed to a second beam splitter, which splits the beam into two portions. The portion of the beam is output to a subsequent optical element in the system. The other portion of the beam exiting the second beam splitter is directed to the second quad cell optical detector for detection.

[0074]

[0088] FIG. 3B provides a schematic diagram of the addition of electrical signal paths in an alignment control system similar to that shown in FIG. 3A. As shown in FIG. 3A, signals from the first and second quad-cell optical detectors are fed separately to ADC / DAC controller, error corrector, and FSM controller components. These components are configured to independently process and analyze the signals from the first and second quad-cell detectors and generate control signals to actuate the first and second fast steering mirrors, thereby providing feedback control of the overall optical alignment. Also shown in FIG. 3B are optical beam paths. FIG. 3C provides a schematic diagram of an example of an intensity pattern illustrating a stable aligned system. FIG. 3D provides a schematic diagram of an example of an intensity pattern illustrating an unstable misaligned system. Thus, by monitoring the intensity pattern quadrature detectors, changes in the optical alignment can be detected and monitored. Such detected changes can further provide a basis for input for closed-loop control of the optical alignment.

[0075]

[0089] FIG. 4 provides a flow chart showing a sequence of steps and criteria for closed-loop feedback control of optical alignment using the quad detector signal and the fast steering mirror (FSM) as inputs to provide controlled optical alignment. The left panel shows the signal analysis and control process in the first fast steering mirror (FSM) and the right panel shows the signal analysis and control process in the second fast steering mirror (FSM). As shown in FIG. 4, beam position data is provided from the quad cell detector and analyzed to identify and / or characterize the occurrence of beam position errors. If a beam position error is identified, a signal is provided to the fast steering mirror and a position correction is generated if necessary. The sequence shown in FIG. 4 is repeated to provide continuous monitoring and correction of the optical alignment.

[0076]

[0090] In one embodiment, for example, if a mirror is used in the light path, the mirror coating can be designed to pass a small amount of the light incident on the mirror. This transmitted beam can impinge on the center of the quad detector. If the beam deviates from its nominal pointing direction, the irradiance in each quadrant of the detector changes. The change in detector irradiance can constitute an error signal that serves to trigger a fine correction motor or the like to restore the intended beam direction by restoring the original light distribution in each quadrant.

[0077]

[0091] Alternatively, a partially reflective beam sampling window can be placed in the beam and direct the reflected light to a quad detector. If a change occurs in the light distribution of the quad detector, a signal can be generated to restore the alignment of the primary beam on the target. One method is to tilt another window in the beam to laterally translate the transmitted beam back to its intended alignment.

[0078]

[0092] Example 3: Interference detection with temperature control

[0093] Thermal stability constraints for an interferometric particle detection system may be primarily driven by optical performance requirements. There are multiple aspects of thermal instability that can affect the functionality of the optical system. Important parameters for thermal stability are the temperature gradient and the overall magnitude of temperature change. Heat sources that affect the performance of the system include heat dissipation from the optics and electronics, and external heat input from the environment. Both causes can change the temperature within the particle detection system, degrading performance. As explained in Example 1, the sensitivity of the instrument gives an indication of the level of temperature change that can be tolerated without affecting performance.

[0079]

[0094] The overall temperature mismatch causes the plate to change length depending on the length scale, the temperature difference, and the thermal expansion coefficient of the material. The equation is given below: d=aLΔT Where: d = total change in length a = thermal expansion coefficient of the material L = length of part ΔT = temperature change

[0080]

[0095] Figure 5 provides a graph of temperature change versus length change over a range of interest (e.g., the length and width of an optical bench). As shown in Figure 6, for a nominal optical tolerance (±0.025mm), the allowable temperature change is on the order of 3°C. Typically, this is the maximum allowable tolerance level for spacing and alignment between many common optical components. There are sections of the optical system where the positional tolerance is on the order of ±0.013mm, thereby further limiting the optimum performance temperature range.

[0081]

[0096] The use of fans in interferometric particle detection systems, a common method for temperature control, can induce vibrations and convection gradients in the air within the system. Pressure and temperature gradients change the refractive index of the air, degrading optical performance. Notably, these temperature gradients are turbulent in nature and, as a result, are not a constant effect that can be counteracted by data manipulation.

[0082]

[0097] To provide thermal control embodiments of certain embodiments of the interferometric particle detection system, active cooling components (e.g., thermoelectric coolers (TECs), etc.) are incorporated that are located on the external housing of the system. These cooling mechanisms are equipped with heat exchange structures and mechanisms (finned heat exchangers, gas purges, etc.) that remove waste heat from the cooling mechanisms and inject it into the external environment. The cooling mechanisms are connected to the internal components of the system using thermal transfer links or heat pipes. This method creates a microenvironment that is both isolated from the external environment and mitigates the effects of internal heat sources. As a result, the performance of the system is more stable than traditional cooling systems that utilize internal cooling fans.

[0083]

[0098] FIG. 6 provides a schematic diagram of a system for interference detection of particles in a fluid stream with a temperature control system. As shown in FIG. 6, a Peltier cooler is provided that is (i) in thermal communication with a heat source, a heat sink, and a temperature sensor via thermal links, and (ii) in electronic communication with the control electronics and the temperature sensor via electrical connections. The schematic diagram shows thermal and electrical connections for controlling temperature in relation to heat sources such as optical, electrical, and / or mechanical components of the optical particle counter. The temperature controller shown in FIG. 6 may be provided as a modular component that is individually thermally coupled to heat sources corresponding to individual heat generating components of the optical particle counter such as optical components (e.g., lasers, mirrors, flow cells, detectors, lenses), electronic components (e.g., processors, controllers, actuators, etc.), or mechanical components (e.g., fans, pumps, etc.). The number of Peltier coolers and / or thermal links depends on the number of heat sources and the cooling capacity of the Peltier cooler.

[0084]

[0099] Without thermal control of critical components within the particle counter, the system may not function properly. For example, optical elements may become misaligned with temperature changes of more than 3 degrees Celsius. Some components, such as lasers, require active cooling to remove heat generated during operation. Chillers or liquid heat exchangers are effective at cooling lasers, but they introduce potential for vibration / noise that can adversely affect ultra-sensitive measurements and increase the overall system footprint, so this is undesirable.

[0085]

[0100] Thermoelectric cooler (TEC) modules, also known as Peltier coolers, bring another thermal management strategy to sensitive particle counters. This technology consists of two semiconductor materials with different electron densities sandwiched between thermally conductive plates. Applying a voltage to the TEC creates a temperature difference between the plates, enabling cooling. When placed in direct contact with the inner or outer walls of a particle counter assembly and / or with individual components such as lasers and detectors, the TEC can manage the temperature of the system.

[0086]

[0101] Advantages of thermal control with TECs include: compact size and elimination of coolant and space required for cooling systems; and a simple design with no moving parts allowing for a longer life for the TEC device.

[0087]

[0102] Example 4: Liquid-phase particle counter with vibration isolation and active temperature control

[0103] This embodiment provides a liquid phase particle counter system with vibration isolation and active temperature control for detecting particles having size dimensions of 100 nm or less, optionally 50 nm or less, and optionally 20 nm or less in a liquid stream, such as a stream of ultrapure water and / or other process liquid. The system includes a flow cell for passing a fluid stream having particles. A probe beam from a light source, such as a laser source, is shaped (e.g., by focusing, stretching, etc.) by beam shaping optics and directed to a flow cell containing the fluid stream, where interaction of the probe beam with particles in the fluid stream generates scattered electromagnetic radiation. A portion of the scattered electromagnetic radiation from the flow cell is collected and directed to a photodetector, such as a detector array, which generates an output signal corresponding to detection of scattered light from the flow cell. Analysis of the output signal, e.g., via a processor, e.g., a firmware and / or software implemented processor, is used to identify and count occurrences of particle detection events, as well as characterize the detected particles in terms of size characteristics, such as effective or average diameter, or classification of particles corresponding to a size range (e.g., below a particular size or within a size range), e.g., via pulse analysis methods such as pulse height analysis, pulse area analysis, etc. By monitoring the scattered light from the flow cell, the number of detected particles is obtained, for example, as a function of time and / or volume of the analyzed fluid.

[0088]

[0104] Figure 7 provides a schematic diagram illustrating an example approach for vibration isolation and cooling in a liquid particle counter system (500). As shown in Figure 7, the components of the system corresponding to the primary vibration source (510), such as a fan, pump, fluid actuator, etc., are directly or indirectly mounted to the housing (520) of the system (500). An optical bench (530), including one or more scientific instruments, such as light sources, beam shaping optics, filters, attenuators, apertures, flow cells, windows, collection optics for scattered light, optical detectors, beam steering and control elements, etc., is at least partially isolated from the housing (520) via one or more vibration isolators (540) to reduce or minimize the transmission rate between the housing (520) and the optical bench (530) to provide vibration isolation. Also shown in FIG. 7 is a cooling module (550) operably connected to the housing (520) for actively and / or passively controlling the temperature of the system (500), including, for example, controlling the temperature of the optical bench (530) and its components to minimize temperature changes during use.

[0089]

[0105] FIG. 8 provides a schematic diagram of a perspective view of the liquid particle counter system (500) showing elements for vibration isolation and temperature control. The internal cooling fan (560) is separate from the optical bench and attached to the housing (520), such as the housing body (520a) and / or the housing lid (520b), and is therefore structurally separated from the optical bench (530). Heat removal from inside the housing is achieved by a separate cooling module (550) attached to the housing (520), such as the lid (520b) and / or the housing body (520a), shown attached to the lid in this embodiment. In one embodiment, for example, the airflow from the cooling module (550) is not directed directly at, directed at, and / or targeted at the optical bench. As shown in FIG. 8, vibration isolators (540) are provided to reduce and / or minimize the transmission of vibrations from the housing (520) to elements of the optical bench (530).

[0090]

[0106] In one embodiment, the cooling module (550) includes an active Peltier thermoelectric cooler operably coupled to the housing (520), for example, via an insulating gasket. Outside the housing, in some embodiments, waste heat from the system is dissipated by contact with a heat transfer medium, for example, using a fan, a roots blower, compressed air, house vacuum, and / or a liquid transfer medium. Inside the housing, in some embodiments, an internal fan assists in the distribution of the heat transfer medium within the housing for heat transfer.

[0091]

[0107] FIG. 9A provides a perspective view of a liquid particle counter system (500) complementary to that of FIG. 8, showing a configuration in which the optical bench (530) is vibrationally isolated from the housing (520) via a vibration isolator (540) that reduces and / or minimizes the transmission of vibrations from the housing (520) to elements of the optical bench (530).

[0092]

[0108] Figure 9B provides an expanded schematic view of the liquid particle counter system (500) showing the components of the vibration isolator (540) and how the vibration isolator (540) is coupled to the optical bench (530). As shown in Figure 9B, adjustable hardware (575), such as brackets and screw / bolt assemblies, are provided to tune the vibration isolation by compressing the nonlinear vibration material isolation layer to minimize the transmission of vibrations of the housing (520) to the optical bench (530). In one embodiment, one or more vibration isolation materials or layers with different properties are provided to isolate the optical bench support (535) from the housing (520) from the vibration source.

[0093]

[0109] As shown in FIG. 9B, a base (580) is provided that comprises a soft material layer, such as an elastomer layer, in which case the optical bench (530) is placed directly or indirectly on the base (580) of the vibration damping system, for example via an optical bench support (535). In some embodiments, a further vibration damping element (590) comprising a soft material layer, such as an elastomer layer, is provided between the optical bench support (535) and a coupling component (595). For example, the coupling component (595) can be configured to mechanically couple the base (580) and the further vibration damping element (590), such as provided by two opposing elastomer layers together on either side of the optical bench support (535). This arrangement allows the structural optical bench support (535) to vibrate freely with respect to at least two vibration layers, including the base (580) and the further vibration damping element (590). In some embodiments, the vibration isolation properties of the two isolation layers, such as the base (580) and the further vibration damping element (590), are adjusted by modifying the vibration isolation layers, for example using adjustable hardware (575) and connecting components (595). This is achieved, for example, by the relative stiffness of the components (595) including clamps and adjustment screws / bolts adjustable hardware (575) that change the dynamic compression modulus. Important parameters in selecting materials for the isolation layers, such as the base (580) and the further vibration damping element (590), include the ratio of the excitation frequency to the natural frequency of the system, the dynamic shear ratio, and the transmissibility.

[0094]

[0110] EMBODIMENTS - The present invention is further described and illustrated by the following embodiments.

[0095]

[0111] Embodiment 1: A flow cell for flowing a fluid containing particles; a light source for generating one or more beams of electromagnetic radiation; beam shaping optics for passing the one or more beams of electromagnetic radiation through the flow cell to produce electromagnetic radiation that is scattered by the particles; at least one optical detector array for receiving electromagnetic radiation from the flow cell, wherein the light source, beam shaping optics, and optical detector array are configured to enable interference detection of the particles and / or optical detection of particles having a size dimension of 100 nm or less; and Equipped with 1. A particle detection system configured such that at least one of temperature, pressure, vibration magnitude, and sonic magnitude, or any combination thereof, is each independently maintained within a selected tolerance range to maintain a high signal-to-noise ratio during the detection of the particle.

[0096]

[0112] Embodiment 2: The system of embodiment 1, wherein the light source, beam shaping optics, and optical detector array are configured to perform structured beam interferometric detection of the particles by passing a structured probe beam of coherent electromagnetic radiation through the flow cell.

[0097]

[0113] Embodiment 3: The system of embodiment 1, wherein the light source, beam shaping optics, and optical detector array are configured to perform heterodyne interferometric detection of the particle by collecting off-axis scattered light and combining the off-axis scattered light with a reference beam to form an interference signal.

[0098]

[0114] Embodiment 4: The system of embodiment 1, wherein the light source and optical detector array are configured to perform single or multi-beam coherent detection of the particles.

[0099]

[0115] Embodiment 5: The system of embodiment 1, wherein the light source and optical detector array are configured to perform structured dark beam interferometric detection of the particles.

[0100]

[0116] Embodiment 6: The system of any of embodiments 1 to 5, wherein the optical detector array is positioned in optical communication with the flow cell to receive incident electromagnetic radiation transmitted through the flow cell and electromagnetic radiation scattered by the particles.

[0101]

[0117] Embodiment 7: The system of embodiment 6, wherein the electromagnetic radiation scattered by the particles comprises forward scattered electromagnetic radiation.

[0102]

[0118] Embodiment 8: The system of embodiment 6 or 7, wherein the incident electromagnetic radiation transmitted through the flow cell and the electromagnetic radiation scattered by the particles undergo constructive and / or destructive optical interference.

[0103]

[0119] Embodiment 9: The system of any of embodiments 1 to 8, wherein the optical detector array is arranged at a scattering angle in the range of 0 degrees to 5 degrees relative to the optical axis of the incident beam.

[0104]

[0120] Embodiment 10: The system of any of embodiments 1 to 9, wherein the optical detector array is arranged at a scattering angle in the range of 0 degrees to 0.5 degrees relative to the optical axis of the incident beam.

[0105]

[0121] Embodiment 11: The system of any of embodiments 1 to 10, wherein the optical detector array is in optical communication with the flow cell to detect interactions of particles and electromagnetic radiation scattered by the particles with an illuminating wavefront.

[0106]

[0122]

[0036] Embodiment 12: The system is configured to: a. A maximum change in T of 5°C at a rate of less than 1°C / hr b. Change in P up to 300 mbar c. Beam path length change of up to 10 mm d. Maximum change in beam focus position of 2 mm e. Maximum 20% change in beam power f. Vibration levels up to 200 microns / sec g. Maximum + / - 5 degree beam angle variation h. Laser noise condition of <2% (RMS) max. i. Maximum laser M<1.3 2 Changes j. Laser linewidth change up to <100 MHz k. Maximum <50% RH change l. Electrical (line power) stability and noise control m. Any combination of these The system of any of embodiments 1 to 11, wherein the system performs interference detection of the particles and / or optical detection of particles having a size dimension of 100 nm or less without significant degradation of the internal particle counting process when exposed to one or more of the following:

[0107]

[0123] Embodiment 13: The system of any of embodiments 1 to 12, wherein the system further comprises a controller operatively coupled to the flow cell, light source, beam shaping optics, optical detector array, or any combination thereof, the controller being adapted to compensate for changes in the system parameters in response to ambient conditions, internal stimuli, external stimuli, or any combination thereof.

[0108]

[0124] Embodiment 14: The system of embodiment 13, wherein the ambient condition, internal stimulus, or external stimulus is selected from the group consisting of a change in temperature, a change in pressure, vibration, sound waves, or any combination thereof.

[0109]

[0125] Embodiment 15: The system of any of embodiments 13 or 14, wherein the controller is a beam alignment system for monitoring the position of the one or more beams of electromagnetic radiation and actively controlling the positioning and / or alignment of a flow cell, a light source, beam shaping optics, an optical detector array, or any combination thereof, so as to maintain a high signal-to-noise ratio during the detection of the particles.

[0110]

[0126] Embodiment 16: The system of embodiment 15, wherein the beam alignment system provides compensation for thermal expansion optical drift.

[0111]

[0127] Embodiment 17: The system of any of embodiments 15 or 16, wherein the beam alignment system provides low frequency vibration compensation.

[0112]

[0128] Embodiment 18: A system of any of embodiments 15 to 17, wherein the beam alignment system provides real-time control of the positioning and / or alignment of a flow cell, a light source, beam shaping optics, an optical detector array, or any combination thereof, within a range of 5 microradians or less at a frequency of 250 Hz or more.

[0113]

[0129] Embodiment 19: The system of any of embodiments 15 to 18, wherein the beam alignment system is a closed loop system.

[0114]

[0130] Embodiment 20: The system of any of embodiments 15 to 19, wherein the beam alignment system comprises one or more optical sensor and actuator systems.

[0115]

[0131] Embodiment 21: The system of embodiment 20, wherein the one or more optical sensors are orthogonal optical sensors disposed in the system, and the actuator system comprises one or more piezoelectrically actuated nanopositioners.

[0116]

[0132] Embodiment 22: The system of any of embodiments 20 or 21, wherein the optical sensor provides an input to the closed loop system and the actuator system provides an output to the closed loop system.

[0117]

[0133] Embodiment 23: The system of any of embodiments 13 to 22, wherein the controller is an isolator or multiple isolators for isolating the flow cell, light source, beam shaping optics, and optical detector array from changes in ambient conditions, internal stimuli, external stimuli of the operating environment, or any combination thereof.

[0118]

[0134] Embodiment 24: The system of embodiment 23, wherein the isolator is a vibration-damping component capable of at least partially preventing the transmission of vibrations from an external operating environment to the system.

[0119]

[0135] Embodiment 25: The system of any of embodiments 23 or 24, wherein the isolator is a vibration-damping component capable of at least partially preventing the transmission of vibrations originating from within the system itself.

[0120]

[0136] Embodiment 26: The system of any of embodiments 24 or 25, wherein the vibration damping component is designed to reduce the transmission of vibrations having a fundamental frequency of 60 Hz or greater to less than 1%.

[0121]

[0137] Embodiment 27: The system of any of embodiments 24 to 26, wherein the vibration damping component comprises a vibration damping spring mechanism, at least two mass dampers, or any combination thereof.

[0122]

[0138] Embodiment 28: The system of embodiment 13, wherein the controller is an active cooling component capable of controlling the temperature of a flow cell, a light source, a beam shaping optics, an optical detector array, or any combination thereof.

[0123]

[0139] Embodiment 29: The system of embodiment 28, wherein the active cooling component is in thermal communication with a flow cell, a light source, a beam shaping optics, an optical bench, an optical detector array, or any combination thereof via a heat transfer link.

[0124]

[0140] Embodiment 30: The system of any of embodiments 28 or 29, wherein the active cooling component comprises a thermoelectric cooler.

[0125]

[0141] Embodiment 31: The system of embodiment 30, wherein the thermoelectric cooler is not in thermal communication with an external housing of the system.

[0126]

[0142] Embodiment 32: The system of any of embodiments 30 or 31, wherein the thermoelectric cooler is provided in thermal communication with a heat exchange structure for removing heat from the thermoelectric cooler and injecting heat into an environment external to the system.

[0127]

[0143] Embodiment 33: The system of embodiment 32, wherein the heat exchange structure is a finned heat exchanger.

[0128]

[0144] Embodiment 34: The system of any of embodiments 30-33, wherein the thermoelectric cooler is purged with a dry gas to prevent moisture condensation on the cooling side.

[0129]

[0145] Embodiment 35: The system of any of embodiments 30-34, wherein the thermoelectric cooler is purged with a dry gas that flows across the hot side heat exchanger to enhance heat dissipation.

[0130]

[0146] Embodiment 36: A system of any of embodiments 1 to 35, wherein the flow cell, light source, beam shaping optics, optical detector array, or any combination thereof, is configured to perform passive separation to compensate for changes in the system parameters in response to ambient conditions, internal stimuli, or external stimuli.

[0131]

[0147] Embodiment 37: The passive separation has the following features: a. Incorporation of one or more vibration isolators b. Incorporation of one or more adhesive layers into the lens c. Incorporation of one or more thermoset or thermoplastic mechanical restraints d. Reducing the size and / or mass of light sources and components e. Incorporation of a lens mount with a natural frequency of 150 Hz or more f. Incorporation of a flow cell that is mechanically isolated from the light source and components g. Thermal expansion coefficient compatible materials h. Low thermal expansion coefficient optical components The system of embodiment 36, wherein the system is performed by one or more of the following:

[0132]

[0148] Embodiment 38: The system of any of embodiments 1 to 37, wherein the light source provides a coherent incident beam.

[0133]

[0149] Embodiment 39: The system of any of embodiments 1 to 38, wherein the light source provides a Gaussian incident beam.

[0134]

[0150] Embodiment 40: The system of any of embodiments 1 to 39, wherein the light source comprises one or more shaping and / or combining optical elements for generating the one or more beams of electromagnetic radiation.

[0135]

[0151] Embodiment 41: The system of embodiment 40, wherein the one or more shaping and / or combining optical elements are diffractive elements, polarizing elements, intensity modulating elements, phase modulating elements, or any combination thereof.

[0136]

[0152] Embodiment 42: The system of any of embodiments 1 to 41, wherein the one or more beams of electromagnetic radiation comprise a structured non-Gaussian beam.

[0137]

[0153] Embodiment 43: The system of embodiment 42, wherein the one or more beams of electromagnetic radiation include a dark beam.

[0138]

[0154] Embodiment 44: The system of any of embodiments 42 or 43, wherein the one or more beams of electromagnetic radiation include a beam characterized by one or more line singularities.

[0139]

[0155] Embodiment 45: The system of any of embodiments 42 or 43, wherein the one or more beams of electromagnetic radiation include an anamorphic beam.

[0140]

[0156] Embodiment 46: The system of any of embodiments 42 to 45, wherein the one or more beams of electromagnetic radiation include a top-hat anamorphic beam.

[0141]

[0157] Embodiment 47: The system of any of embodiments 1 to 46, wherein the optical detector array comprises a plurality of segmented linear or two-dimensional arrays of detectors.

[0142]

[0158] Embodiment 48: The system of any of embodiments 1 to 47, wherein at least one optical detector array enables differential detection.

[0143]

[0159] Embodiment 49: The system of any one of embodiments 1 to 48, wherein the fluid is a liquid or a gas.

[0144]

[0160] Embodiment 50: The system of any of embodiments 1 to 49, wherein the system is for detecting particles in a liquid chemical.

[0145]

[0161] Embodiment 51: The system of any of embodiments 1 to 50, wherein the system is for detecting particles in ultrapure water.

[0146]

[0162] Embodiment 52: The system of any of embodiments 1 to 49, wherein the system is for detecting particles in a high pressure gas.

[0147]

[0163] Embodiment 53: The system of any of embodiments 1 to 49, wherein the system is for detecting particles on a surface.

[0148]

[0164] Embodiment 54: A method for detecting particles in a fluid, comprising: providing a flow of said fluid containing particles; generating one or more beams of electromagnetic radiation using a light source; passing the one or more beams of electromagnetic radiation through the flow cell using beam shaping optics to generate electromagnetic radiation that is scattered by the particles; directing electromagnetic radiation from the flow cell to an optical detector array to provide interferometric detection of the particles and / or optical detection of particles having size dimensions of 100 nm or less; Including, A method wherein a flow cell, a light source, a beam shaping optics, an optical detector array, or any combination thereof, are configured and / or controlled to maintain a high signal-to-noise ratio during the detection of the particles.

[0149]

[0165] Embodiment 53: The method of embodiment 54, wherein the optical detector array is positioned in optical communication with the flow cell to receive incident electromagnetic radiation transmitted through the flow cell and electromagnetic radiation scattered by the particles.

[0150]

[0166] Embodiment 54: The method of embodiment 55, wherein the electromagnetic radiation scattered by the particles comprises forward scattered electromagnetic radiation.

[0151]

[0167] Embodiment 55: The method of either embodiment 55 or 56, wherein the incident electromagnetic radiation transmitted through the flow cell and the electromagnetic radiation scattered by the particles undergo constructive and / or destructive optical interference.

[0152]

[0168] Embodiment 56: The method of any of embodiments 54 to 57, wherein the optical detector array is arranged at a scattering angle in the range of 0 degrees to 5 degrees relative to the optical axis of the incident beam.

[0153]

[0169] Embodiment 57: The method of any of embodiments 54 to 58, wherein the optical detector array is arranged at a scattering angle within the range of 0 degrees to 0.5 degrees relative to the optical axis of the incident beam.

[0154]

[0170] Embodiment 58: The method of any of embodiments 54 to 59, wherein the optical detector array is provided in optical communication with the flow cell to detect interactions of the particles and electromagnetic radiation scattered by the particles with an illuminating wavefront.

[0155]

[0171] Embodiment 59: The method further comprises the steps of: a. A maximum change in T of 5°C at a rate of less than 1°C / hr b. Change in P up to 300 mbar c. Beam path length change of up to 10 mm d. Maximum change in beam focus position of 2 mm e. Maximum 20% change in beam power f. Vibration levels up to 200 microns / sec g. Maximum + / - 5 degree beam angle variation h. Laser noise condition of <2% (RMS) max. i. Maximum laser M<1.3 2 Changes j. Laser linewidth change up to <100 MHz k. Maximum <50% RH change l. Electrical (line power) stability and noise control m. Any combination of these 61. The method of any of embodiments 54 to 60, wherein the method performs interference detection of the particles and / or optical detection of particles having a size dimension of 100 nm or less without significant degradation of the internal particle counting process when exposed to one or more of the following:

[0156] INCORPORATION BY REFERENCE AND VARIATION STATEMENT

[0172] All references cited throughout this application, e.g., patent documents, including issued or granted patents or equivalents, patent application publications, and non-patent literature documents or other materials, are incorporated by reference in their entirety into this application to the extent that each reference is at least partially consistent with the disclosure of this application, as if each reference was individually incorporated by reference (e.g., a partially-conflicting reference is incorporated by reference except for the partially-conflicting portion of the reference).

[0157]

[0173] The following patents and patent applications relate to interferometric particle detection using structured beams and are incorporated by reference in their entireties: U.S. Pat. No. 7,746,469, U.S. Patent Application Publication No. 20170176312, WO 2019 / 082186, and WO 62 / 838,835.

[0158]

[0174] The terms and expressions used in this specification are used as terms of description, not as terms of limitation, and are not intended to exclude the equivalents of the features shown and described or portions thereof, but are recognized to be capable of various modifications within the scope of the invention as described in the claims. 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 may be used by those skilled in the art, and such modifications and variations are considered to be within the scope of this invention as defined by the appended claims. The specific embodiments provided herein are examples of useful embodiments of the invention, and as will be appreciated by those skilled in the art, the invention can be implemented using numerous variations of the devices, device components, and method steps described in this specification. Also, as will be appreciated by those skilled in the art, the methods and devices useful for the methods can include numerous optional configuration and processing elements and steps.

[0159]

[0175] As used herein and in the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, a reference to a "cell" includes a plurality of such cells and equivalents thereof known to those of skill in the art. Similarly, the terms "a" (or "an"), "one or more," and "at least one" can be used interchangeably herein. It should also be noted that the terms "comprise," "include," and "have" can also be used interchangeably. The phrase "of any of claims XX-YY" (where XX and YY refer to claim numbers) is intended to provide multiple dependent claims in an alternative format, and in some embodiments, is interchangeable with the phrase "in any one of claims XX-YY."

[0160]

[0176] When a group of substitutes is disclosed herein, it is understood that all individual members of that group and all subgroups are separately disclosed. When Markush groups or other groups are used herein, all individual members of the group and all possible combinations and subcombinations of the group are intended to be individually included in the disclosure.

[0161]

[0177] Any device, system, formulation, combination of components, or method described or exemplified herein can be used to practice the present invention, unless otherwise stated.

[0162]

[0178] Whenever a range, e.g., a temperature range, a time range, or a composition or concentration range, is given in the specification, all intermediate ranges and subranges, as well as all individual values ​​that fall within the given range, are intended to be included in the disclosure. It is understood that any subrange or individual value within a range or subrange included in the description herein may be excluded from the claims herein.

[0163]

[0179] All patents and publications mentioned in this specification are indicative of the level of skill of those skilled in the art to which this invention pertains. It is intended that the references cited herein are incorporated herein in their entirety by reference to indicate the state of the art as of their publication or filing date, and that this information may be used herein, as appropriate, to exclude certain embodiments that are in the prior art. For example, when a composition of matter is claimed, it should be understood that compounds known and available in the art prior to the applicant's invention are not intended to be included in the composition of matter claims herein, including compounds given the enabling disclosure in the references cited herein.

[0164]

[0180] As used herein, "comprising" is synonymous with "including," "including," or "characterized by," and is inclusive or open-ended, not excluding further unrecited elements or method steps. As used herein, "consisting of" excludes any element, step, or ingredient not defined 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 instance 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 be practiced in the absence of any element or elements, or any limitation or limitations not specifically disclosed herein.

[0165]

[0181] As will be appreciated by those skilled in the art, starting materials, biological materials, reagents, synthesis methods, purification methods, analysis methods, analytical 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 art-known functional equivalents of such materials and methods are intended to be included in this 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 invention as claimed. 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 can be used by those skilled in the art, and that such modifications and variations are considered to be within the scope of the invention as defined by the appended claims.

Claims

1. a flow cell for flowing a fluid containing particles; a light source for generating one or more beams of electromagnetic radiation; beam shaping optics for passing the one or more beams of electromagnetic radiation through the flow cell to produce electromagnetic radiation that is scattered by the particles; at least one optical detector array for receiving electromagnetic radiation from the flow cell, wherein the light source, the beam shaping optics, and the optical detector array are configured to enable interferometric detection of the particles and / or optical detection of particles having a size dimension of 100 nm or less; and an optical bench, wherein the flow cell, the light source, the beam shaping optics, and the at least one optical detector array are supported by the optical bench; a housing surrounding the optical bench such that the optical bench is thermally isolated from an external environment; an active temperature control system comprising a closed-loop temperature control system configured to control a temperature of the light source, the closed-loop temperature control system comprising a thermoelectric cooler and a temperature sensor thermally coupled to the light source, and a temperature controller in electrical communication with the thermoelectric cooler and the temperature sensor, the temperature controller configured to control a temperature of the light source; Equipped with the active temperature control system is configured to control a temperature of an interior volume of the enclosure that contains the optical bench; 1. A particle detection system configured such that at least one of temperature, pressure, vibration magnitude, and sonic magnitude, or any combination thereof, is each independently maintained within a selected tolerance range to maintain a high signal-to-noise ratio during the detection of the particles.

2. 2. The particle detection system of claim 1 , wherein the light source, the beam shaping optics, and the optical detector array are configured to perform structured beam interferometric detection of the particles by passing a structured probe beam of coherent electromagnetic radiation through the flow cell.

3. 2. The particle detection system of claim 1, wherein the light source, the beam shaping optics, and the optical detector array are configured to perform heterodyne interferometric detection of the particle by collecting off-axis scattered light and combining the off-axis scattered light with a reference beam to form an interference signal.

4. The particle detection system of claim 1 , wherein the light source and the optical detector array are configured for single or multi-beam coherent detection of the particles.

5. The particle detection system of claim 1 , wherein the light source and the optical detector array are configured for structured dark beam interferometric detection of the particles.

6. 6. The particle detection system of claim 1, wherein the optical detector array is disposed in optical communication with the flow cell to receive incident electromagnetic radiation transmitted through the flow cell and electromagnetic radiation scattered by the particles.

7. The particle detection system of claim 6 , wherein the electromagnetic radiation scattered by the particle comprises forward scattered electromagnetic radiation.

8. 8. A particle detection system according to claim 6 or 7, wherein the incident electromagnetic radiation transmitted through the flow cell and the electromagnetic radiation scattered by the particles undergo constructive and / or destructive optical interference.

9. A particle detection system according to any preceding claim, wherein the optical detector array is provided at a scattering angle in the range of 0 degrees to 5 degrees relative to the optical axis of the incident beam.

10. A particle detection system according to any one of claims 1 to 9, wherein the optical detector array is provided at a scattering angle in the range of 0 degrees to 0.5 degrees relative to the optical axis of the incident beam.

11. 11. The particle detection system of claim 1, wherein the optical detector array is provided in optical communication with the flow cell for detecting interactions of the particles and electromagnetic radiation scattered by the particles with an illumination wavefront.

12. The system satisfies the following conditions: i. A maximum change in T of 5° C. at a rate of less than 1° C. / hr ii. Change in P up to 300 mbar iii. Beam path length change of up to 10 mm iv. Beam focus position change of up to 2 mm v. Beam power change of up to 20% vi. Vibration levels up to 200 microns / sec vii. Maximum + / - 5 degree beam angle variation viii. Laser noise condition of <2% (RMS) maximum ix. Maximum laser M<1.3 ２ Changes x. Laser linewidth changes up to <100 MHz xi. Maximum <50% change in RH xii. Electrical (line power) stability and noise control xiii. Any combination of these 12. A particle detection system according to claim 1, wherein the particle detection system provides for interferometric detection of particles and / or optical detection of particles having a size dimension of 100 nm or less without significant degradation of an internal particle counting process when exposed to one or more of:

13. 13. The particle detection system of claim 1, further comprising a controller operatively coupled to the flow cell, the light source, the beam shaping optics, the optical detector array, or any combination thereof, the controller for compensating for changes in the system parameters in response to ambient conditions, internal stimuli, external stimuli, or any combination thereof.

14. 14. The particle detection system of claim 13, wherein the ambient condition, the internal stimulus, or the external stimulus is selected from the group consisting of a change in temperature, a change in pressure, a vibration, a sound wave, or any combination thereof.

15. 15. The particle detection system of claim 13 or 14, wherein the controller is a beam alignment system for monitoring a position of the one or more beams of electromagnetic radiation and actively controlling the positioning and / or alignment of the flow cell, the light source, the beam shaping optics, the optical detector array, or any combination thereof, so as to maintain a high signal-to-noise ratio during the detection of the particles.

16. 16. The particle detection system of claim 15, wherein the beam alignment system provides compensation for thermal expansion optical drift.

17. 17. A particle detection system according to claim 15 or 16, wherein the beam alignment system provides low frequency vibration compensation.

18. 18. The particle detection system of claim 15, wherein the beam alignment system provides real-time control of positioning and / or alignment of the flow cell, the light source, the beam shaping optics, the optical detector array, or any combination thereof, within a range of 5 microradians or less at a frequency of 250 Hz or greater.

19. A particle detection system according to any one of claims 15 to 18, wherein the beam alignment system is a closed loop system.

20. A particle detection system according to any one of claims 15 to 19, wherein the beam alignment system comprises one or more optical sensor and actuator systems.

21. 21. The particle detection system of claim 20, wherein the one or more optical sensors are orthogonal optical sensors disposed in the system, and the actuator system comprises one or more piezoelectrically actuated nanopositioners.

22. 22. A particle detection system according to claim 20 or 21, wherein the optical sensor comprises an input to a closed loop system and the actuator system provides an output to the closed loop system.

23. 23. The particle detection system of any one of claims 13 to 22, wherein the controller is an isolator or multiple isolators for isolating the flow cell, the light source, the beam shaping optics, and the optical detector array from changes in ambient conditions, internal stimuli, external stimuli of an operating environment, or any combination thereof.

24. 24. A particle detection system as claimed in claim 23, wherein the isolator is a vibration damping component capable of at least partially preventing the transmission of vibrations from an external operating environment to the system.

25. 25. A particle detection system according to claim 23 or 24, wherein the isolator is a vibration-damping component capable of at least partially preventing the transmission of vibrations originating from within the system itself.

26. 26. A particle detection system according to claim 24 or 25, wherein the vibration damping component is designed to reduce the transmission of vibrations having a fundamental frequency of 60 Hz or greater to less than 1%.

27. A particle detection system according to any one of claims 24 to 26, wherein the vibration damping component comprises a vibration damping spring mechanism, at least two mass dampers, or any combination thereof.

28. 14. The particle detection system of claim 13, wherein the controller is an active cooling component capable of controlling a temperature of the flow cell, the light source, the beam shaping optics, the optical detector array, or any combination thereof.

29. 30. The particle detection system of claim 28, wherein the active cooling component is in thermal communication with the flow cell, the light source, the beam shaping optics, the optical bench, the optical detector array, or any combination thereof via a heat transfer link.

30. 30. A particle detection system according to claim 28 or 29, wherein the active cooling component comprises a thermoelectric cooler.

31. 31. A particle detection system as claimed in claim 30, wherein the thermoelectric cooler is not in thermal communication with an external housing of the system.

32. 32. A particle detection system according to claim 30 or 31, wherein the thermoelectric cooler is provided in thermal communication with a heat exchange structure for removing heat from the thermoelectric cooler and injecting heat into an environment external to the system.

33. 33. A particle detection system as claimed in claim 32, wherein said heat exchange structure is a finned heat exchanger.

34. A particle detection system according to any one of claims 30 to 33, wherein the thermoelectric cooler is purged with a dry gas to prevent moisture condensation on the cooling side.

35. A particle detection system according to any one of claims 30 to 34, wherein the thermoelectric cooler is purged with a dry gas flowing across a hot side heat exchanger to enhance heat dissipation.

36. 36. The particle detection system of claim 1, wherein the flow cell, the light source, the beam shaping optics, the optical detector array, or any combination thereof, are configured to provide passive isolation to compensate for changes in the system parameters in response to ambient conditions, internal stimuli, or external stimuli.

37. The passive separation has the following characteristics: i. Incorporation of one or more vibration isolators ii. Incorporation of one or more adhesive layers into the lens iii. Incorporation of one or more thermoset or thermoplastic mechanical restraints iv. Reducing the size and / or mass of light sources and components v. Incorporation of a lens mount with a natural frequency of 150 Hz or more vi. Incorporation of a flow cell that is mechanically isolated from the light source and components vii. Thermal expansion coefficient matching material viii. Low thermal expansion coefficient optical components 37. The particle detection system of claim 36, wherein the particle detection system is performed by one or more of:

38. A particle detection system according to any preceding claim, wherein the light source provides a coherent incident beam.

39. A particle detection system according to any preceding claim, wherein the light source provides a Gaussian incident beam.

40. A particle detection system according to any one of the preceding claims, wherein the light source comprises one or more shaping and / or combining optical elements for producing the one or more beams of electromagnetic radiation.

41. 41. The particle detection system of claim 40, wherein the one or more shaping and / or combining optical elements are diffractive elements, polarizing elements, intensity modulating elements, phase modulating elements, or any combination thereof.

42. A particle detection system according to any preceding claim, wherein the one or more beams of electromagnetic radiation comprise structured non-Gaussian beams.

43. 43. The particle detection system of claim 42, wherein the one or more beams of electromagnetic radiation comprise a dark beam.

44. 44. A particle detection system as claimed in claim 42 or 43, wherein the one or more beams of electromagnetic radiation comprise a beam characterized by one or more line singularities.

45. 44. A particle detection system as claimed in claim 42 or 43, wherein the one or more beams of electromagnetic radiation comprise an anamorphic beam.

46. A particle detection system according to any one of claims 42 to 45, wherein the one or more beams of electromagnetic radiation comprise a top hat anamorphic beam.

47. A particle detection system according to any preceding claim, wherein the optical detector array comprises a plurality of segmented linear or two-dimensional arrays of detectors.

48. A particle detection system according to any preceding claim, wherein the at least one optical detector array enables differential detection.

49. A particle detection system according to any preceding claim, wherein the fluid is a liquid or a gas.

50. A particle detection system according to any one of claims 1 to 49, wherein the system is for detecting particles in a liquid chemical.

51. A particle detection system according to any one of claims 1 to 50, wherein the system is for detecting particles in ultra-pure water.

52. A particle detection system according to any one of claims 1 to 49, wherein the system is for detecting particles in a high pressure gas.

53. A particle detection system according to any one of the preceding claims, wherein the system is for detecting particles on a surface.

54. 1. A method for detecting particles in a fluid, comprising: providing a flow of said fluid containing particles; generating one or more beams of electromagnetic radiation using a light source; passing the one or more beams of electromagnetic radiation through the flow cell using beam shaping optics to generate electromagnetic radiation that is scattered by the particles; directing electromagnetic radiation from the flow cell to an optical detector array to provide interferometric detection of the particles and / or optical detection of particles having size dimensions of 100 nm or less; providing an optical bench supporting the flow cell, the light source, the beam shaping optics, and the at least one optical detector array; providing an enclosure surrounding the optical bench such that the optical bench is thermally isolated from an external environment; controlling a temperature of the light source with an active temperature control system comprising a closed-loop temperature control system including a thermoelectric cooler and a temperature sensor thermally coupled to the light source, and a temperature controller in electrical communication with the thermoelectric cooler and the temperature sensor, the temperature controller configured to control a temperature of the light source; controlling a temperature of an interior volume of the enclosure containing the optical bench with the active temperature control system; Including, The method, wherein the flow cell, the light source, the beam shaping optics, the optical detector array, or any combination thereof, are configured and / or controlled to maintain a high signal-to-noise ratio during the detection of the particles.

55. 55. The method of claim 54, wherein the optical detector array is positioned in optical communication with the flow cell to receive incident electromagnetic radiation transmitted through the flow cell and electromagnetic radiation scattered by the particles.

56. 56. The method of claim 55, wherein the electromagnetic radiation scattered by the particles comprises forward scattered electromagnetic radiation.

57. 57. The method of claim 55 or 56, wherein the incident electromagnetic radiation transmitted through the flow cell and the electromagnetic radiation scattered by the particles undergo constructive and / or destructive optical interference.

58. A method according to any one of claims 54 to 57, wherein the optical detector array is provided at a scattering angle in the range of 0 degrees to 5 degrees relative to the optical axis of the incident beam.

59. A method according to any one of claims 54 to 58, wherein the optical detector array is provided at a scattering angle in the range of 0 degrees to 0.5 degrees relative to the optical axis of the incident beam.

60. 60. The method of any one of claims 54 to 59, wherein the optical detector array is provided in optical communication with the flow cell for detecting interactions of the particles and electromagnetic radiation scattered by the particles with an illuminating wavefront.

61. The method comprises the steps of: i. A maximum change in T of 5° C. at a rate of less than 1° C. / hr ii. Change in P up to 300 mbar iii. Beam path length change of up to 10 mm iv. Beam focus position change of up to 2 mm v. Beam power change of up to 20% vi. Vibration levels up to 200 microns / sec vii. Maximum + / - 5 degree beam angle variation viii. Laser noise condition of <2% (RMS) maximum ix. Maximum laser M<1.3 ２ Changes x. Laser linewidth changes up to <100 MHz xi. Maximum <50% change in RH xii. Electrical (line power) stability and noise control xiii. Any combination of these 61. The method of any one of claims 54 to 60, wherein the method provides for interferometric detection of particles and / or optical detection of particles having a size dimension of 100 nm or less without significant degradation of an internal particle counting process when exposed to one or more of:

Images