Liquid impinger sampling system and method

Abstract

A liquid impinger is disclosed. The liquid impinger includes a nozzle disposed therein and attached to a bottom portion. In some embodiments, the liquid impinger includes a polymeric material. Also disclosed is a method of constructing a liquid impinger, the method including forming at least two components, assembling them into a liquid impinger, filling the liquid impinger with a liquid, and sterilizing the filled liquid impinger by exposing it to radiation prior to use. Also disclosed is a method of using a liquid impinger by conveying a gas containing a test substance in the liquid impinger and transferring at least a portion of the test substance from the gas to the containing liquid. The method further includes culturing and / or detecting at least a portion of the test substance in the liquid after transferring the test substance from the gas to the liquid without removing the liquid from the liquid impinger.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001]

[0001] This application claims the benefit of priority to U.S. Provisional Patent Application No. 63 / 220,176, filed July 9, 2021, the entire contents of which are incorporated herein by reference. [Background technology]

[0002]

[0002] The present invention is generally in the field of particle sampling, collection and analysis. The present invention relates generally to apparatus and methods for sampling and characterizing particles in air and gases, including process chemicals, for applications including the assessment of viable biological contaminants in a variety of cleanroom and manufacturing environments.

[0003]

[0003] Monitoring gas streams for the presence of contaminants, including viable biological particles, is important in many industries, including pharmaceuticals and biologicals, food and beverages, and cosmetics, where the presence of particles, even at very low levels, can adversely affect the manufacturing process and the integrity or quality of the product. Furthermore, regulatory requirements and industry standards include the establishment and maintenance of low particle levels that meet the requirements of relevant process condition certifications. For example, in pharmaceutical and biological manufacturing, contamination with airborne particles consisting of viable biological contaminants puts therapeutic products at risk due to health and safety concerns that require compliance with strict standards set by the U.S. Food and Drug Administration (FDA) as well as other foreign and international health regulatory agencies.

[0004] To address the impact of particulate contamination, cleanrooms and cleanzones are commonly employed in a variety of manufacturing and fabrication environments and facilities where the presence and quantity of particles and other contaminants are actively monitored and documented. Standards for classifying cleanroom particle levels and for testing and monitoring to ensure compliance are provided by ISO 14664-1 and 14664-2. Aerosol optical particle counters are commonly used to determine airborne particle contamination levels in cleanrooms and cleanzones, while liquid particle counters are used to optically measure particle contamination levels in process gases. Where microbial particles are of special interest, such as in the pharmaceutical and biological products industries, not only is it important to quantify the number of airborne particles, but characterizing the viability and identity of microbial particles is also an issue. ISO 14698-1 and 14698-2 provide standards for the evaluation of cleanroom and cleanzone environments for biological contaminants.

[0005]

[0005] Various liquid impingers and methods are known for collection, analysis, and monitoring for the presence of viable biological particles in gas streams in cleanroom applications, such as settling plates, contact plates, surface swabbing, fingertip sampling, agar-filled Petri dishes, impactor-based samplers, and liquid impingers. For these types of biological particle collection and analysis techniques, various operational aspects are important to ensure efficient collection, detection, and analysis. For example, if biological particles cannot be detected as being present in the cleanroom air, collection efficiency can be very important since the cleanroom environment may be contaminated at a level higher than detection. If it is determined that an undercount has occurred, pharmaceutical products made in these environments may be identified as not meeting required standards, resulting in costly product recalls. Similarly, undercounts can occur if the collection process does not maintain the viability of the collected biological particles. This situation can occur, for example, if the collected biological particles are destroyed, damaged, or rendered non-viable during collection and growth, such that the collected particles are not replicated in the culture process and are subsequently unidentifiable.

[0006]

[0006] At the other extreme, false positives can occur, resulting in an overestimation of the concentration of biological particles. Overcounts of this nature occur when biological particles that are not collected from the cleanroom air but are placed in contact with the growth media are able to replicate in the incubation process and are inappropriately identified as originating from the cleanroom air. Conditions that contribute to false positives include lack of proper sterilization of the collection media and collection system prior to particle collection, and improper handling of the growth media by cleanroom personnel during loading into and / or removal from the particle collection system and loading into the incubator. Again, a pharmaceutical product can be identified as not meeting the required criteria. Without sufficient measures to identify false positives, such conditions can indicate that a pharmaceutical product does in fact meet the required criteria, but that the criteria are not met, as destroyed by the overestimation of the concentration of biological particles in the cleanroom air.

[0007]

[0007] While some solutions, such as disposable agar-filled Petri dishes and disposable impactors, allow for non-contact of the media throughout the growth / culture step, detection or recognition is often performed manually, subject to potential contamination from human manipulation / intervention, and thus may result in false positives. For example, disposable impactor-based samplers, such as those described in U.S. Pat. No. 10,345,200, provide disposable impactor-based air samplers designed to allow for sterilization, sampling collection, and / or readout in a fully integrated configuration, making them less susceptible to false positives. However, the time required to culture or grow sampled microorganisms in agar Petri dishes and disposable impactors is typically several days, which may result in unnecessary delays between sampling and receiving the culture results.

[0008]

[0008] Liquid impingers provide a versatile sampling platform for sampling biological particles as well as molecular contaminants. These devices work by flowing a gas (e.g., air, process gas, or gas mixture) through an absorbent material, such as a liquid absorbent material, and removing it after exposure to the gas for a set period of time to perform external testing, such as post-incubation testing and / or identification, characterization, and / or quantification of contaminants transferred from the gas to the absorbent material by chemical methods such as PCR, mass spectrometry, and / or chromatography. For example, U.S. Patent Application Publication No. 2021 / 0063349 provides an impinger-based sampling system that uses a real-time analyzer that allows triggered detection and characterization of contaminants in gas samples and environments by meeting certain real-time criteria.

[0009]

[0009] Conventional impinger systems are susceptible to a variety of failures. For example, known impingers are typically constructed of glass and therefore are not consumable (i.e., disposable). They must be cleaned and sterilized prior to each repeated use. This extra cleaning and sterilization process creates the potential for contamination, especially if it is not sufficient. Furthermore, known liquid impingers are often too large to allow for ideal placement at the monitoring point, as a large liquid impinger is required to contain a sufficient volume of liquid growth medium to mitigate evaporation due to the sampling process.

[0010]

[0010] Thus, there remains a need for sampling systems and methods that can provide sufficient sampling of viable biological particles. For example, there is a need for particle collection systems for cleanroom and manufacturing applications that provide high particle collection efficiency while maintaining the viability of collected biological particles. There is also a need for particle collection systems for cleanroom and manufacturing applications that reduce the occurrence of false positive events. Summary of the Invention

[0011]

[0011] The present invention generally provides devices and methods for sampling, detecting, and / or characterizing analytes in gases, such as particulate and / or molecular analytes. For example, in some embodiments, the present invention provides devices and methods for sampling, collecting, and analyzing live biological particles, such as microorganisms, and molecular contaminants. The devices and methods of the present invention include impingers and bubblers for collecting and / or analyzing analytes, such as particulate and / or molecular contaminants, in manufacturing environments requiring low levels of contaminants, such as clean rooms and sterile environments. The devices and methods of the present invention include disposable impingers and bubblers that allow for filling, sterilization, use, and / or readout in a fully integrated configuration to minimize or completely eliminate risks associated with user handling, such as generating false positives due to contamination during the sampling, particle growth, and / or analysis process. The devices and methods of the present invention include disposable impingers and bubblers that include polymeric materials (e.g., polymeric materials that can be produced by molding, extrusion, vacuum forming, 3D printing, and subtractive manufacturing and / or polymeric materials that are at least partially optically transparent in the visible spectral region).

[0012] In some embodiments, the present disclosure provides a method for producing a medicament for the treatment of a cancer, comprising: a vessel including a vertical axis, an upper portion, an interior portion, and a lower portion including an interior base; a gas inlet disposed within the interior and in fluid communication with the interior through at least one nozzle attached to the lower portion, the nozzle including a nozzle opening; and a gas outlet in fluid communication with the interior; 1. A liquid impinger comprising: the gas inlet, the at least one nozzle, the interior, and the gas outlet, in turn, define a gas flow path; A fluid impinger is disclosed in which a container is configured to contain a fluid therein.

[0013] In one embodiment, the container includes a sampling port configured to selectively access liquid within the interior of the container to allow sampling of the liquid in the container. In one embodiment, the container includes a removable cap for sealing the sampling port. In one embodiment, the cap includes a septum configured to receive a needle to allow withdrawal of liquid from the interior of the container while maintaining the interior of the container sealed.

[0014] In some embodiments, the present disclosure provides a method for producing a medicament for the treatment of a cancer, comprising: A liquid impinger according to any preceding aspect or a vessel including a vertical axis, an upper portion, an interior portion containing a liquid, and a lower portion including an interior base; a gas inlet disposed within the interior and in fluid communication with the interior through at least one nozzle attached to the lower portion, the nozzle including a nozzle opening, the nozzle opening being submerged in the liquid; and a gas outlet in fluid communication with the interior; providing a liquid impinger comprising a gas inlet, at least one nozzle, an interior, and a gas outlet, which in turn define a gas flow path; conveying a gas containing the test substance along a gas flow path until contacting the liquid, optionally within the liquid; transferring at least a portion of the test substance from the gas to the liquid, optionally the test substance comprises a particle, a molecular test substance, or a combination thereof, and further optionally, in some embodiments, the test substance comprises a biological particle; A method is disclosed that includes:

[0015] In one embodiment, the method may include the step of withdrawing a sample of the liquid from the interior of the container through a sampling port in response to the step of moving, hi one embodiment, the step of withdrawing the sample includes inserting a needle into a septum of the sample port.

[0016] In some embodiments, a method for generating a liquid impinger includes the steps of: forming at least two components of a liquid impinger; Optionally, creating an assembled liquid impinger by assembling at least two components, the assembled liquid impinger comprising: a vessel including a vertical axis, an upper portion, an interior portion, and a lower portion including an interior base; a gas inlet disposed within the interior and in fluid communication with the interior through at least one nozzle attached to the lower portion, the nozzle including a nozzle opening; and a gas outlet in fluid communication with the interior; Equipped with the gas inlet, the at least one nozzle, the interior, and the gas outlet, in turn, define a gas flow path; a container configured to contain a liquid therein; Optionally, filling a portion of the interior of the assembled liquid impinger with liquid to create a filled liquid impinger; Optionally, exposing the filled liquid impinger to radiation to sterilize at least a portion of the liquid present within the liquid impinger, thereby producing a filled and sterile liquid impinger; Optionally, either before or after the exposing step, packaging the filled liquid impinger or the filled and sterile liquid impinger in a manner that prevents ingress of particles or contamination into the interior of the liquid impinger; A method is disclosed that includes:

[0017] In some embodiments, a method for producing a filling and sterilizing liquid impinger includes the steps of: forming at least two components of a liquid impinger; creating an assembled liquid impinger by assembling at least two components, the assembled liquid impinger comprising: a vessel including a vertical axis, an upper portion, an interior portion, and a lower portion including an interior base; a gas inlet disposed within the interior and in fluid communication with the interior through at least one nozzle attached to the lower portion, the nozzle including a nozzle opening; and a gas outlet in fluid communication with the interior; the gas inlet, the at least one nozzle, the interior, and the gas outlet, in turn, define a gas flow path; a container configured to contain a liquid therein; filling a portion of an interior of the assembled liquid impinger with liquid to create a filled liquid impinger; exposing the filled liquid impinger to radiation to sterilize at least a portion of the liquid present within the liquid impinger, thereby producing a filled and sterile liquid impinger; Optionally, either before or after the exposing step, packaging the filled liquid impinger or the filled and sterile liquid impinger in a manner that prevents ingress of particles or contamination into the interior of the liquid impinger; A method is disclosed that includes:

[0018] In some embodiments, a method for producing a filling and sterilizing liquid impinger includes the steps of: A first providing step includes providing a filled liquid impinger, the filled liquid impinger comprising: a vessel including a vertical axis, an upper portion, an interior portion, and a lower portion including an interior base; a gas inlet disposed within the interior and in fluid communication with the interior through at least one nozzle attached to the lower portion, the nozzle including a nozzle opening; and a gas outlet in fluid communication with the interior; Equipped with the gas inlet, the at least one nozzle, the interior, and the gas outlet, in turn, define a gas flow path; a container containing a liquid therein; exposing the filled liquid impinger to radiation to sterilize at least a portion of the liquid present within the liquid impinger, thereby producing a filled and sterile liquid impinger; Optionally, either before or after the exposing step, packaging the filled liquid impinger or the filled and sterile liquid impinger in a manner that prevents ingress of particles or contamination into the interior of the liquid impinger; A method is disclosed that includes:

[0019] In some embodiments, the liquid impinger of the present systems and methods is a sampler, collector, or analyzer for an analyte, such as a particulate and / or molecular analyte. In some embodiments, the liquid impinger of the present systems and methods is an impinger or bubbler for sampling an analyte, such as a particulate and / or molecular analyte. In some embodiments, the method is for sampling, characterizing, and / or monitoring an analyte in a gas, optionally the analyte includes a particle, such as a biological or non-biological particle, or a molecular analyte, such as a molecular contaminant, impurity, or process chemical, or any combination thereof.

[0020]

[0020] Without being bound by any particular theory, a discussion of the beliefs or understandings of the underlying principles related to the devices and methods disclosed herein is provided herein, and it is recognized that an embodiment of the present invention can be effective and useful, regardless of the ultimate correctness of any mechanistic explanation or hypothesis. [Brief description of the drawings]

[0021] [Figure 1] 1A-1C show some aspects of a liquid impinger, particularly a liquid impinger for sampling gas, with a nozzle disposed inside and attached to the bottom, and a gas inlet connected to the nozzle by a tube running from the top to the bottom inside; [Diagram 2]2A-2C show some embodiments of a liquid impinger similar to FIG. 1, except that the tubes supplying gas are approached from the bottom of the liquid impinger, rather than tubes running through the interior. [Diagram 3] 2A-2C show various embodiments of a liquid impinger similar to FIG. 1, except with additional liquid, an extension, and a tapered portion. [Figure 4] 4A-4D show several embodiments of liquid impingers similar to FIG. 3, except with differently shaped extensions and less steep tapers. [Diagram 5] 5A-5C show various embodiments of liquid impingers similar to FIG. 4, except that they have a lower portion that is shaped differently and do not have an extension located above the lower portion. [Figure 6A] FIG. 1 shows an embodiment of a liquid impinger that is similar to the liquid impingers shown in other figures, except for, for example, different internal base shapes, nozzle configurations, and / or mounting shapes between the gas supply tube and the nozzle(s). [Figure 6B] FIG. 1 shows an embodiment of a liquid impinger that is similar to the liquid impingers shown in other figures, except for, for example, different internal base shapes, nozzle configurations, and / or mounting shapes between the gas supply tube and the nozzle(s). [Figure 6C] FIG. 1 shows an embodiment of a liquid impinger that is similar to the liquid impingers shown in other figures, except for, for example, different internal base shapes, nozzle configurations, and / or mounting shapes between the gas supply tube and the nozzle(s). [Figure 6D] FIG. 1 shows an embodiment of a liquid impinger that is similar to the liquid impingers shown in other figures, except for, for example, different internal base shapes, nozzle configurations, and / or mounting shapes between the gas supply tube and the nozzle(s). [Figure 7A] FIG. 1 illustrates one embodiment of a nozzle configuration that is helpful in understanding the definition of the term "horizontal angle" found elsewhere in this specification. [Figure 7B]FIG. 1 illustrates one embodiment of a nozzle configuration that is helpful in understanding the definition of the term "horizontal angle" found elsewhere in this specification. [Figure 8] FIG. 1 illustrates aspects of a nozzle configuration that are helpful in understanding the definition of the term "vertical angle" found elsewhere in this specification. [Figure 9] FIG. 4 shows a detailed version of a liquid impinger similar to FIG. 3. [Figure 10] FIG. 10 is an exterior view of the liquid impinger of FIG. [Figure 11] 1 is a flow diagram of several aspects of a method for generating a liquid impinger. [Figure 12] FIG. 1 illustrates a three component liquid impinger with outlines showing each separate component. [Figure 13A] 1 is a perspective view of a liquid impinger showing an exemplary angular orientation of the gas inlets and tubes relative to the nozzles. FIG. [Figure 13B] 1 is a perspective view of a liquid impinger showing an exemplary angular orientation of the gas inlets and tubes relative to the nozzles. FIG. [Figure 14A] 1 is a top view illustrating an exemplary angular orientation of the nozzles of the liquid impinger. [Figure 14B] 1 is a top view illustrating an exemplary angular orientation of the nozzles of the liquid impinger. [Figure 15A] FIG. 2 is a cross-sectional view of the liquid impinger. [Figure 15B] FIG. 2 is a side cutaway view of the liquid impinger. [Figure 15C] FIG. 2 is a top view of the fluid impinger. Naming convention description

[0022]

[0036] Generally, the terms and phrases used herein have their respective art-recognized meanings, which can be found by reference to standard texts, journal references, and background understood by those of ordinary skill in the art. The following definitions are provided to clarify their specific use in the context of the present invention.

[0023]

[0037] As used herein, "analyte" refers to one or more species, compositions, or materials to be sampled, detected, monitored, and / or analyzed. Analytes may refer to atoms, ions, clusters, and molecular species, or may refer to particles (including biological and non-biological particles). In some embodiments, the analyte is a trace component, impurity, and / or contaminant of a gas, such as a trace component, impurity, and / or contaminant of a liquid, gas, or any mixture thereof, including water, air, solvents, solutions, process liquid chemicals, process gases, gases or liquids from a manufacturing and / or processing environment or process. In one embodiment, the analyte is present in a gas to be monitored, such as a gas or liquid from a sample, process, or environment to be monitored (such as a clean room or clean zone environment). In one embodiment, the analyte is a particle, optionally a biological particle, such as a living biological particle. In one embodiment, the analyte is a molecular analyte.

[0024]

[0038] The term "particle" or "particles" refers to minute objects that are often treated as contaminants. Particles can be, but are not necessarily, any material that is produced by the action of friction, for example, when two surfaces are in mechanical contact and there is mechanical movement. Particles can be single components or can 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" can also refer to biological particles, such as bacteria, fungi, archaea, protists, viruses, spores, and microorganisms, including other single-celled microorganisms. Biological particles include, but are not limited to, microorganisms with a particle size of 0.1-20 μm. Biological particles include viable biological particles that are capable of reproduction, for example, upon cultivation in a growth medium. For example, in some embodiments, 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. Particles may also refer to minute objects capable of collection, detection, characterization, and / or identification by a particle sampler, collector, or detector, such as an impinger, impactor, bubbler, or particle counter. Particles may also refer to any minute object that can be detected by an optical particle counter because it absorbs or scatters light. As used herein, "particle" or "particles" is intended to exclude individual atoms or molecules of a carrier gas or sample medium (e.g., water, air, process liquid chemicals, process gases, nitrogen, oxygen, carbon dioxide, etc.). In some embodiments, particles may initially be present on a surface, such as a tool surface in a microfabrication facility or a production surface in a pharmaceutical manufacturing facility, and may be analyzed in the gas after being released from the surface. Some embodiments of the invention are capable of sampling, collecting, detecting, sizing, and / or counting particles, including aggregates of material having sizes greater than 50 nm, 100 nm, 1 μm or greater, or 10 μm or greater.In some embodiments, the particles include particles having a size selected from 50 nm to 50 μm, a size selected from 100 nm to 10 μm, or a size selected from 500 nm to 5 μm.

[0025]

[0039] As used herein, the term "particle size" refers to the average or effective diameter of a particle, the average or effective length of a particle, the average or effective width of a particle, the equivalent spherical diameter of a particle (the diameter of a sphere of equivalent volume), or the largest dimension of a particle, as the context indicates.

[0026]

[0040] The expression "molecular analyte" refers to an analyte including atoms, ions, clusters, and molecular species. Molecular analytes include molecular contaminants, impurities, process chemicals, trace elements, and the like. In one embodiment, the molecular analyte includes one or more acids, such as HF, HCl, HBr, HNO3, H2SO4, H3PO4, HCOOH, and CH3COOH, or any combination thereof. In one embodiment, the molecular analyte includes one or more bases, such as NH3, methylamine, dimethylamine, ethylamine, and N-methyl-2-pyrrolidone, or any combination thereof. In one embodiment, the molecular analyte includes one or more volatile organic compounds, such as CH3OH, isopropyl alcohol, propylene glycol monomethyl ether acetate (PGMEA), and hexamethyldisilazane, or any combination thereof.

[0027]

[0041] As used herein, "impinger" refers to a container, passage, or vessel for receiving a gas and trapping, collecting, and / or transforming the analyte by contacting the analyte in the gas with the impinger medium. Impingers useful in the present systems and methods may house or incorporate a variety of impinger media for trapping, collecting, and / or transforming the analyte, including one or more liquids (including solutions), gels, and / or sols. In some embodiments, the impinger is a "bubbler," a device that agitates or bubbles a liquid, such as a solution or solvent, by flowing a gas through the impinger. In some embodiments, the impinger includes an impinger medium that includes a layer, film, droplet, or matrix of liquid, solution, sol, and / or gel material. Impingers may be fabricated from leachable materials to reduce the generation of species, such as ions, molecules, or particles, that may arise from the impinger itself or its components and that may interfere with the subsequent detection and / or analysis of the collected, trapped, or transformed analyte.

[0028]

[0042] The expression "sampling a particle" broadly refers to the collection of particles, for example in a gas stream from an environment to be monitored. Sampling in this context includes the movement of particles in the gas stream to a collector, collection medium, and / or growth medium (e.g., liquid medium in an impinger or bubbler), or impact surface of an impactor. Alternatively, sampling may refer to the transport of particles in the gas to a particle analysis area, for example for optical detection and / or characterization. Sampling may also refer to the collection of particles having one or more preselected characteristics, such as size (e.g., cross-sectional dimension, such as diameter, effective diameter, etc.), particle type (biological or non-biological, viable or non-viable, etc.), or particle composition. Sampling may optionally include analysis of the collected particles, for example by subsequent optical, imaging, or visual analysis. Sampling may also optionally include the growth of viable biological particles for the sample, for example by a culture process with a growth medium. A sampler refers to a device for sampling analytes, such as particle and / or molecular analytes.

[0029]

[0043] The phrase "detecting a particle" broadly refers to the sensing, identification of the presence or absence, and / or characterization of a particle. In some embodiments, detecting a particle refers to counting the particles. In some embodiments, detecting a particle refers to characterization and / or measurement of a physical property of a particle, such as diameter, cross-sectional dimension, shape, size, aerodynamic size, or any combination thereof. In some embodiments, detecting a particle refers to visualization, visual counting, and / or optical imaging of the particles. A particle counter is a device for counting particles in a gas or gas volume, and may optionally also allow characterization of the particles based on, for example, size (e.g., cross-sectional dimension such as diameter or effective diameter), particle type (e.g., biological or non-biological), or particle composition. An optical particle counter is a device that detects particles by measuring the scattering, emission, or absorption of light by the particles.

[0030]

[0044] The term "polymeric material" refers to a macromolecule composed of repeating structural units linked by covalent bonds or a polymerization product of one or more monomers, often characterized by a large molecular weight. The term "polymeric material" includes homopolymers, i.e., polymers consisting essentially of a single repeating monomeric subunit. The term "polymeric material" also includes copolymers, i.e., polymers consisting essentially of two or more monomeric subunits, such as, for example, random, block, alternating, segmented, graft, tapered, and other copolymers. As used herein, the term "polymeric material" does not include glasses or ceramics.

[0031]

[0045] "Polymer" refers to a macromolecule composed of repeating structural units linked by covalent bonds or a polymerization product of one or more monomers, and is often characterized by a large molecular weight. The term polymer includes homopolymers, i.e., polymers consisting essentially of a single repeating monomer subunit. The term polymer also includes copolymers, i.e., polymers consisting essentially of two or more monomer subunits, such as random, block, alternating, segmented, graft, tapered, and other copolymers. Useful polymers include organic or inorganic polymers that may be amorphous, semi-amorphous, crystalline, or partially crystalline. Crosslinked polymers with linked monomer chains are particularly useful for some applications. Polymers that can be used in the above methods, devices, and components include, but are not limited to, plastics, elastomers, thermoplastic elastomers, elastoplastics, thermoplastics, and acrylates. Exemplary polymers include, but are not limited to, acetal polymers, biodegradable polymers, cellulose polymers, fluoropolymers, nylons, polyacrylonitrile polymers, polyamide-imide polymers, polyimides, polyarylates, polybenzimidazoles, polybutylenes, polycarbonates, polyesters, polyetherimides, polyethylene, polyethylene copolymers and modified polyethylenes, polyketones, poly(methyl methacrylate), polymethylpentene, polyphenylene oxide and polyphenylene sulfide, polyphthalamides, polypropylenes, polyurethanes, styrenics, sulfone-based resins, vinyl-based resins, rubbers (including natural rubber, styrene-butadiene, polybutadiene, neoprene, ethylene-propylene, butyl, nitrile, silicone), acrylics, nylons, polycarbonates, polyesters, polyethylene, polypropylene, polystyrene, polyvinyl chloride, polyolefins, or any combination thereof.

[0032]

[0046] The term "horizontal angle" (θ) refers to the angle formed between (1) the horizontal component of the nozzle direction as viewed along the vertical axis and (2) the tangent where the horizontal component of the nozzle direction intersects the sidewall. The nozzle direction only includes its horizontal component. In other words, to the extent the nozzle is angled either up or down along the vertical axis, such vertical component is not considered in determining the horizontal angle. Referring to FIG. 7A is useful in understanding the meaning of "horizontal angle" (θ). In this regard, the horizontal component of the nozzle direction 717 is determined by viewing the nozzle along the vertical axis from a top-to-bottom perspective (as shown in FIG. 7A) and placing an imaginary plane (i.e., horizontal plane) perpendicular to the vertical axis through the center of the nozzle opening and drawing a line in this horizontal plane that represents the horizontal component of the nozzle direction (feature 717). Also, the location where this horizontal plane passes through the sidewall is the relevant portion of the sidewall for determining the tangent 718, and not the location where the nozzle direction actually intersects the sidewall when considering the vertical component or gas velocity. The angle between the horizontal component 717 of the nozzle direction in this horizontal plane and the tangent 718 is the horizontal angle θ. This definition is appropriate for spherical, cylindrical, elliptical, and other curved sidewalls. In situations where the sidewall is a different shape, such as a polygon, the tangent is determined to the smallest circle that fits the shape, such as a polygon, as shown in FIG. 7B. Other features of FIG. 7B are the same as FIG. 7A. It should be noted that while FIGS. 7A and 7B are useful in understanding the concept of "horizontal angle," they should be viewed as examples only, as they are not mathematically accurate and certain features, such as tangents, are not necessarily shown as perfect tangents.

[0033]

[0047] The term "vertical angle" (φ) refers to the angle formed between a plane perpendicular to the vertical axis (i.e., a horizontal plane) and the nozzle direction when viewed from a direction perpendicular to the vertical axis and the nozzle direction. FIG. 8 is useful for understanding the vertical angle (φ). FIG. 8 shows a lower portion 803, a nozzle 808, a nozzle opening 809, a vertical axis 801, and a horizontal plane 820 perpendicular to the vertical axis 801. To better reveal the details of the vertical angle, FIG. 8 shows an enlarged view of the nozzle / nozzle opening and the nozzle direction. The nozzle 808 is viewed from a direction perpendicular to the vertical axis 801 and the nozzle direction 819. The angle (φ) formed between the plane 820 and the nozzle direction 819 when viewed from this perspective is the "vertical angle" (φ). A positive vertical angle indicates the nozzle direction is pointing up (i.e., above the horizontal plane), a negative vertical angle indicates the nozzle direction is pointing away from the top (i.e., below the horizontal plane), and a vertical angle of 0° indicates the nozzle direction is in the horizontal plane (i.e., pointing neither up nor away from the top). As with Figures 7A and 7B, the features of Figure 8 should be considered as illustrative only, as they are not mathematically accurate.

[0034]

[0048] "Fluid communication" refers to a configuration of two or more objects that allows for the transport, passage, or flow of gas from one object to another. For example, in some embodiments, two objects are in fluid communication with each other if there is a gas flow path directly between the two objects. In some embodiments, two objects are in fluid communication with each other if there is an indirect gas flow path between the two objects, such as involving one or more other objects or flow paths between the two objects. For example, in one embodiment, components of a particle impinger are in fluid communication with each other, such as one or more of a gas inlet, gas outlet, interior, nozzle, tube, restricted flow opening, pressure sensor, flow generator, etc. In one embodiment, two objects present in a gas are not necessarily in fluid communication with each other without the entrainment, passage, and / or flow of gas from the first object to the second object along a flow path, etc.

[0035]

[0049] "Flow rate" refers to the amount of gas flowing through a defined point or area, such as the inlet or gas outlet of a particle impinger or bubbler. In one embodiment, flow rate refers to mass flow rate, i.e., the mass of gas flowing through a defined point or area. In one embodiment, flow rate refers to volumetric flow rate, i.e., the volume of gas flowing through a defined point or area.

[0036]

[0050] When numerical values ​​(e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10) are disclosed herein, such values ​​will typically be followed by the following sentence: "Each of these values ​​can be preceded or followed by the terms 'about', 'at least', 'at least about', 'less than', or 'less than about', and any of the above values ​​can be used alone to express single-pointed or open-ended ranges or in combination to express multiple single-pointed or closed-ended ranges." This statement allows for each of the aforementioned numerical values ​​to be used alone (e.g., 4), preceded by the word "about" (e.g., about 8), preceded by the phrase "at least about" (e.g., at least about 2), preceded by the phrase "at least" (e.g., at least 10), followed by the phrase "less than" (e.g., less than 1), placed before or after the phrase "less than about" (e.g., less than about 7), or in any combination with or without any of the preceding or following words or phrases to define the range (e.g., 2 to 9, about 1 to 4, at least 3, 8 to about 9, 8 to less than 10, about 1 to about 10, etc.). Furthermore, when a range is expressed as "about X or less," this expression is the same as a range that is otherwise a combination of "about X" and "less than about X." For example, "about 10 or less" is the same as "about 10, or less than about 10." Such interchangeable range descriptions are contemplated herein. Although other range formats may be disclosed herein, the difference in format should not be construed as implying the existence of a substantial difference.

[0037]

[0051] As used herein, the term "about" means that small variations from the stated value will give substantially the same results as the stated value. In situations where this definition is not applicable or is extremely difficult to apply, the term "about" means a deviation (either positive or negative) of 10% from the stated value. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0038]

[0052] In the following description, numerous specific details are set forth regarding the devices, components, and methods of the present invention in order to fully explain 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.

[0039]

[0053] The liquid impingers and bubbler liquid impingers, systems, and methods disclosed herein provide various benefits. For example, the use of a liquid medium allows for easier detection of particles such as microorganisms with less handling (and therefore less risk of contamination from human contact) as well as faster growth of such microorganisms during the incubation step. Also, the use of a sterile, closed device (which may be disposable) minimizes or prevents false positives. Furthermore, the design and method of use of the liquid impinger allows for longer monitoring times while minimizing the size of the liquid impinger, since the high velocity gas flow does not destroy the microorganisms and minimizes the loss of liquid during sampling. For example, the use of multiple nozzles allows for a larger overall gas flow while reducing the gas velocity at each nozzle, thus preventing the death or disruption of the microorganisms. Furthermore, in some embodiments, certain nozzle features, such as the nozzle angle and size, increase the horizontal velocity component of the gas flow and minimize the vertical velocity component, thereby creating vortices in the liquid and maximizing the gas / liquid interaction time, thereby transferring a relatively large amount of particles from the gas to the liquid. Additionally, in some aspects, the nozzle design alone or in conjunction with the design of the liquid impinger walls can reduce liquid loss due to evaporation, thereby reducing the liquid work that the liquid impinger must do during operation, thereby allowing for a smaller overall size of the liquid impinger and facilitating placement in sampling locations where space is at a premium.

[0040]

[0054] In some embodiments, the present disclosure provides: a vessel including a vertical axis, an upper portion, an interior portion, and a lower portion including an interior base; a gas inlet disposed within the interior and in fluid communication with the interior through at least one nozzle attached to the lower portion, the nozzle including a nozzle opening; and a gas outlet in fluid communication with the interior; Equipped with the gas inlet, the at least one nozzle, the interior, and the gas outlet, in turn, define a gas flow path; A fluid impinger is disclosed in which a container is configured to contain a fluid therein.

[0041]

[0055] In some embodiments, the liquid impinger is constructed of any suitable material. In some embodiments, the material comprises, consists of, or consists essentially of at least one polymeric material. In some embodiments, the polymeric material includes organic polymers that may be amorphous, semi-amorphous, crystalline, or partially crystalline. Cross-linked polymers are particularly useful for some applications. Polymers that can be used in the methods, systems, liquid impingers, devices, and components include, but are not limited to, plastics, elastomers, thermoplastic elastomers, elastoplastics, thermoplastics, and acrylates. Exemplary polymers include acetal polymers, biodegradable polymers, cellulose polymers, fluoropolymers, nylon, polyacrylonitrile, poly(acrylonitrile-butadiene-styrene), polyimide-imide polymers, polyimides, acrylics, polyacrylates, polybenzimidazoles, polybutylenes, polycarbonates, polyesters, polyetherimides, polyethylene, polyethylene copolymers and modified polyethylenes, polyketones, poly(alkyl)(alkyl)acrylates (such as poly(methyl methacrylate)), polymethylpentenes, polyphenylene oxides, and polyphenylene oxides. Examples of suitable polyolefins include, but are not limited to, phenylene sulfide, polyphthalamide, polypropylene, polyurethane (e.g., thermoplastic polyurethane), clear polystyrene (e.g., Polystyrol™ available from BASF), polystyrene, high impact polystyrene, styrenics, sulfone-based resins, vinyl-based resins, rubber (including natural rubber, thermoplastic rubber, styrene-butadiene, polybutadiene, neoprene, ethylene-propylene, butyl, nitrile, silicone), polyvinyl chloride, polyoxymethylene, polyolefins, or any combination thereof.In some embodiments, the polymeric material comprises poly(acrylonitrile-butadiene-styrene), polyethylene, polycarbonate, polyamide (nylon), polystyrene, clear polystyrene (e.g., Polystyrol™ available from BASF), high impact polystyrene, polypropylene, polyoxymethylene, polyurethane (e.g., thermoplastic polyurethane), rubber (e.g., thermoplastic rubber), or any combination thereof. In some embodiments, the liquid impinger does not comprise glass or ceramic. In some embodiments, the liquid impinger is not composed of a material that comprises glass or ceramic. In some embodiments, at least a portion of the liquid impinger comprises glass or ceramic.

[0042]

[0056] In some embodiments, various benefits are associated with liquid impingers that include, consist of, consist essentially of, or are formed from at least one polymeric material. Such benefits include, for example, (1) the transparency of the polymeric material to radiation for the purpose of sterilizing at least a portion of the interior of the liquid impinger (and / or at least a portion of any liquid contained therein), (2) the ability of the liquid impinger to be manufactured, for example, by molding, extrusion, additive manufacturing, or subtractive manufacturing to enable mass production, as well as the details of the resulting liquid impinger, for example, with respect to the location and configuration of the nozzle, (3) the inertness of the polymeric material (e.g., no deleterious effects on or killing of any biological particles that migrate from gas to liquid), (4) disposability of the liquid impinger (e.g., by recycling or landfill disposal), (5) cost-effectiveness (e.g., the costs associated with purchasing and / or forming, such as by molding, a polymeric material into a liquid impinger is less than the processes required to form the glass or ceramic in the desired shape at the desired detail and in the appropriate location with the associated nozzle), or (6) any combination thereof. In any event, in some embodiments, the liquid impinger comprises glass and / or ceramic.

[0043]

[0057] In some embodiments, the liquid impinger comprises any suitable amount of polymeric material. In some embodiments, the liquid impinger comprises 50, 55, 60, 65, 70, 75, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 weight percent of polymeric material. Each of the above numbers can be preceded or followed by the words "about," "at least," "at least about," "less than," or "less than about," and any of the above numbers can be used alone to represent a single point or open-ended range or in combination to represent multiple single points or closed-ended ranges. For example, in some embodiments, the liquid impinger comprises at least 50, 75-98, at least 90, or 65-88 weight percent of polymeric material.

[0044]

[0058] In some embodiments, the liquid impinger further comprises a liquid. In some embodiments, the liquid is a liquid growth medium. In some embodiments, the liquid comprises, consists of, or consists essentially of water. In some embodiments, the liquid (e.g., liquid growth medium) comprises, consists of, or consists essentially of tryptic soy broth (TSB), oil, mineral oil, VIATRAP available from SKC, Inc., R2A broth available from HIMEDIA, or any combination thereof. In some embodiments, the liquid further comprises an additive. In some embodiments, the additive is or comprises a surfactant, an antifoaming agent, or a combination thereof. In some embodiments, the additive is or comprises lecithin. In some embodiments, the additive is or comprises an antifoaming agent. In some embodiments, the liquid comprises an antifoaming agent. In some embodiments, the antifoaming agent is a C16-C18 ethoxylated propoxylated alcohol (e.g., CAS# 68002-96-0 or CPL2908 from Silitex, SRL). In some embodiments, the antifoaming agent (e.g., a C16-C18 ethoxylated propoxylated alcohol) is used in the liquid in an amount of 0.001% to 1% by volume (e.g., 0.001% to 0.01%, 0.01% to 0.1%, 0.1% to 0.5%, or 0.5% to 1% by volume). In some embodiments, the surfactant is an ionic surfactant, a non-ionic surfactant, or a combination thereof. In some embodiments, the surfactant is a TWEEN, such as TWEEN 80, a polysorbate, such as polysorbate 20, 40, 60, 80, or any combination thereof. In some embodiments, the liquid comprises VIATRAP, available from SKC, Inc. In some embodiments, the liquid comprises TSB, lecithin, and TWEEN 80. In some embodiments, the liquid comprises R2A broth. In some embodiments, the liquid impinger does not contain liquid (e.g., during manufacture prior to filling with liquid, shipping, and / or sale to an end user).

[0045]

[0059] In some embodiments, the liquid employed in the liquid impinger does not form an emulsion when gas passes through the liquid impinger along the gas flow path (e.g., bubbling gas (e.g., air or sample gas) through the liquid). In some embodiments, the formation of emulsions can be prevented by the use of one or more surfactants and / or antifoaming agents.

[0046]

[0060] In some embodiments, such as when the liquid impinger contains a liquid, at least one nozzle is submerged in the liquid and conveys the gas along the gas flow path, thereby passing the gas through the liquid. In some embodiments, the placement of the at least one nozzle at the bottom of the liquid impinger maximizes the flow path of the gas, including particles, through the liquid impinger and maximizes the gas / liquid interaction time, thereby maximizing the amount of particles transferred from the gas to the liquid. In some embodiments, the gas includes particles. In some embodiments, the particles include at least one microorganism or virus. In some embodiments, the particles include bacteria, spores, or combinations thereof. In some embodiments, the at least one nozzle is attached to the bottom (e.g., via an internal base, a sidewall, or combinations thereof). In some embodiments, the at least one nozzle is not directly attached to the bottom, but is indirectly attached to the bottom, for example, via a feature such as a tube. In some embodiments, the at least one nozzle is not attached to the bottom. In some embodiments, the at least one nozzle is not attached to the bottom, and the gas inlet is connected to the at least one nozzle by a tube that runs internally from the top to the bottom. In some embodiments, at least one nozzle is not attached to the lower portion, and the gas inlet is connected to the at least one nozzle via a tube approaching the lower portion from the side or below, rather than via a tube located inside.

[0047]

[0061] In some embodiments, the liquid impinger is produced by any suitable process. In some embodiments, the liquid impinger is produced by a process including molding, injection molding, blow molding, rotational molding, additive manufacturing, 3D printing, subtractive manufacturing, casting, molding, vacuum forming, extrusion, or any combination thereof, optionally where the process produces at least three separate components joined together to form the liquid impinger. In some embodiments, the process includes injection molding. In some embodiments, the process includes additive manufacturing, such as 3D printing. In some embodiments, the process includes injection molding and additive manufacturing.

[0048]

[0062] In some embodiments, the liquid impinger comprises optional components. In some embodiments, the liquid impinger comprises at least three separate components joined together to form the liquid impinger. In some embodiments, the liquid impinger comprises three components (e.g., a third component including a lower portion, a base, and a top portion). In some embodiments, the liquid impinger comprises four, five, six, or seven components. In some embodiments, the liquid impinger comprises one or more caps configured to be attached to the gas inlet and gas outlet, respectively. In some embodiments, the one or more caps are in place on the gas inlet and gas outlet before and / or after use of the liquid impinger for gas sampling to prevent unwanted contamination from air from entering the liquid impinger.

[0049]

[0063] In some embodiments, the liquid impinger can be assembled from two or more components in any suitable manner. In some embodiments, the lower portion is configured to be attached to or removed from the liquid impinger by screw-type rotation along threads on the lower portion of the liquid impinger. In some embodiments, the two or more components (e.g., including the lower portion) are configured to be attached to the liquid impinger by sliding (e.g., forming a slip fit), snap-fitting, clicking-fitting, or any other suitable manner. In some embodiments, after such attachment, the components are secured in their respective attached configurations by heat (e.g., melting), adhesives, or a combination thereof.

[0050]

[0064] In some embodiments, the liquid impinger comprises any suitable number of nozzles. In some embodiments, the liquid impinger comprises at least one nozzle. In some embodiments, the at least one nozzle comprises at least two nozzles, at least three nozzles, at least four nozzles, at least five nozzles, at least six nozzles, or at least seven nozzles. In some embodiments, the liquid impinger comprises two, three, four, five, six, or seven nozzles. In some embodiments, the liquid impinger comprises three nozzles.

[0051]

[0065] In some embodiments, the nozzle may have a nozzle opening of any suitable size. In some embodiments, the nozzle opening has a diameter (mm) of 0.01, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.2, 1.4, 1.6, 1.8, 2, 2.2, 2.4, 2.6, 2.8, 3, 3.2, 3.4, 3.6, 3.8, 4, 4.5, or 5. Each of the above values ​​may be preceded or followed by the words "about", "at least", "at least about", "less than", or "less than about", and any of the above values ​​may be used alone to represent a single point or open-ended range or in combination to represent multiple single points or closed-ended ranges. For example, in some embodiments, the nozzle has a diameter of 0.1 to 3.2, 0.05 to 2.8, or less than 2.6. If the liquid impinger has multiple nozzles, each nozzle may have the same diameter or may have different diameters. In cases where the nozzle opening is not circular, the numbers above represent the diameter of the smallest circle that contains the opening.

[0052]

[0066] In some embodiments, the nozzles may have any suitable shape. In some embodiments, at least one nozzle includes a shape that includes a circular arc. In some embodiments, the nozzle shape describes the shape of the nozzle inside the liquid impinger. For example, in some embodiments, at least one nozzle is attached to a tube that extends from the top to the bottom inside the liquid impinger, and the nozzle shape describes the shape of the portion of the nozzle that extends from the tube to the nozzle opening. In some embodiments, the nozzle shape is determined when viewed along a vertical axis. In some embodiments, at least one nozzle includes a shape that includes a circular arc, and the arc is substantially in a plane that forms an angle of 85° to 95°, 80° to 100°, about 90°, or 90° with the vertical axis. In some embodiments, the nozzle in the shape of a circular arc avoids the gas flow exiting the nozzle opening from directly and strongly impinging on the sidewall (e.g., at an angle of 90° or 80 to 100°), but rather promotes a swirling motion of the liquid inside, causing the gas flow to impinge on the sidewall at a relatively shallow angle. In some embodiments, when a plane meets one or more of these angles, the vertical component of the gas flow is minimized, promoting swirling of the liquid and extended gas / liquid interaction time, rather than angling the gas flow toward the surface or interior base of the liquid.

[0053]

[0067] In some embodiments, the gas inlet is connected to at least one nozzle in any suitable manner. In some embodiments, the gas inlet is connected to at least one nozzle by a tube that runs internally from top to bottom. In some embodiments, the gas inlet is connected to at least one nozzle by a tube that does not run internally from top to bottom. For example, in some embodiments, the gas inlet is connected to at least one nozzle by a tube that is close to the bottom or attached to the bottom, but such a tube is not located inside the liquid impinger. In some embodiments, the gas inlet is connected to at least one nozzle by a tube that is located just below, to the side, or both of the bottom of the liquid impinger.

[0054]

[0068] In some embodiments, the tube may have any suitable shape (including, for example, straight, curved, helical, substantially straight, substantially curved, substantially helical, or any combination thereof). In some embodiments, the shape of the tube is relative to a vertical axis. In some embodiments, the tube is substantially straight along the vertical axis. In some embodiments, the tube is substantially helical along the vertical axis. In some embodiments, the tube is substantially curvilinear.

[0055]

[0069] In some embodiments, the gas flow path is bent at any suitable angle between the tube and at least one nozzle. For example, in some embodiments, the gas flow path is bent at an angle of X° between the tube and at least one nozzle, where X (°) is 75, 80, 85, 90, 95, 100, or 105. Each of the above values ​​can be preceded or followed by the words "about", "at least", "at least about", "less than", or "less than about", and any of the above values ​​can be used alone to represent a single point or open-ended range, or in combination to represent multiple single points or closed-ended ranges. For example, in some embodiments, the gas flow path is bent at an angle of 80° to 100°, 75° to 105°, or at least 85° between the tube and at least one nozzle.

[0056]

[0070] In some embodiments, the nozzle opening has any suitable shape. In some embodiments, the shape of the nozzle opening is circular, oval, triangular, rectangular, pentagonal, hexagonal, polygonal, star, or irregular. When the liquid impinger employs two or more nozzles, each nozzle can have the same or different nozzle opening shapes. For example, in some embodiments, the liquid impinger includes two or more nozzles, and each nozzle opening of the two or more nozzles is the same (e.g., circular). In some embodiments, the liquid impinger includes two or more nozzles, and each nozzle opening of the two or more nozzles is different (e.g., some nozzle openings are oval and some nozzle openings are polygonal). All combinations of nozzle shapes are contemplated herein.

[0057]

[0071] In some embodiments, at least one nozzle has any suitable horizontal angle (θ). In some embodiments, the horizontal angle (θ) (°) is 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 45, 46, 48, or 50. Each of the above values ​​can be preceded or followed by the words "about", "at least", "at least about", "less than", or "less than about", and any of the above values ​​can be used alone to represent a single point or open-ended range, or in combination to represent multiple single points or closed-ended ranges. For example, in some embodiments, the horizontal angle (θ) (°) is 0 to 40, less than 45, 4 to 24, or 10 to 30. In some embodiments, when multiple nozzles are present, each nozzle can have any of the aforementioned horizontal angles independently, and thus can have the same horizontal angle or different horizontal angles.

[0058]

[0072] In some embodiments, at least one nozzle has any suitable vertical angle (φ). In some embodiments, the vertical angle (φ) (°) is -45, -44, -42, -40, -38, -36, -34, -32, -30, -28, -26, -24, -22, -20, -18, -16, -14, -12, -10, -8, -6, -4, -2, 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, or 45. Each of the above numerical values ​​may be preceded or followed by the words "about", "at least", "at least about", "less than", or "less than about", and any of the above numerical values ​​may be used alone to represent a single point or open-ended range, or in combination to represent multiple single points or closed-ended ranges. For example, in some embodiments, the vertical angle (φ) (°) is -40 to 40, 0, -10 to 0, 0 to 10, 8 to 18, or -6 to 6. In some embodiments, when multiple nozzles are present, each nozzle may independently have any of the above-mentioned vertical angles, and therefore may have the same vertical angle or different vertical angles.

[0059]

[0073] In some embodiments, at least one nozzle has any suitable combination of horizontal angle (θ) and vertical angle (φ). The combination can be any vertical angle disclosed herein and any horizontal angle disclosed herein. For example, in some embodiments, the horizontal angle (°) is 0-45 and the vertical angle (°) is -40-40, the horizontal angle (°) is 0-30 and the vertical angle is -10-10, or the horizontal angle (°) is 4-34 and the vertical angle is 0-12.

[0060]

[0074] In some embodiments, the lower portion further comprises a sidewall. In some embodiments, the sidewall is a cylinder, a sphere, an ellipse, or a polygonal shape as described elsewhere herein. In some embodiments, the lower portion further comprises a sidewall, and the nozzle opening is disposed within a suitable distance of the sidewall. In some embodiments, the lower portion further comprises a sidewall, and the nozzle opening is disposed substantially flush with the sidewall. As used herein, "flush" with the sidewall refers to a situation in which the surface defining the nozzle opening is shared with the sidewall of the lower portion. Thus, a nozzle opening "substantially flush" with the sidewall includes this "flush" situation, while also including an embodiment in which the nozzle opening is separated from the sidewall by a very short and insignificant distance. In some embodiments, the nozzle opening is located within a distance (mm) of X of the sidewall, where X is 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 17, 18, 19, or 20. Each of the above values ​​may be preceded or followed by the words "about", "at least", "at least about", "less than", or "less than about", and any of the above values ​​may be used alone to represent a single point or open-ended range, or in combination to represent multiple single points or closed-ended ranges. For example, in some embodiments, the distance (mm) is 0 to 10, 0 to 5, 1.5 to 12.5, less than 10, or less than 8. In some embodiments, the lower portion further comprises a sidewall, and the nozzle opening is disposed within 10 mm of the sidewall or substantially flush with the sidewall.

[0061]

[0075] In some embodiments, the lower portion of the liquid impinger may comprise any suitable shape. For example, in some embodiments, the lower portion comprises a cylindrical wall extending along at least a portion of a substantially vertical axis. In some embodiments, the lower portion is cylindrical. In some embodiments, the lower portion comprises a substantially spherical or elliptical shape. In some embodiments, the lower portion comprises a bulb or rounded-bottom shape. In some embodiments, the lower portion comprises a polygonal shape. In some embodiments, the lower portion comprises a polygonal shape extending along at least a portion of a substantially vertical axis.

[0062]

[0076] In some embodiments, the interior comprises an internal base. In some embodiments, the internal base can have any suitable shape. In some embodiments, the internal base is flat or substantially flat in a direction perpendicular to the vertical axis. In some embodiments, the internal base is convex, concave, spherical, or elliptical. In some embodiments, the internal base is pyramidal.

[0063]

[0077] In some embodiments, the liquid impinger further comprises at least one extension between the lower portion and the upper portion, the extension having a greater internal cross-sectional area at its maximum widening point than the internal cross-sectional area at the maximum widening point of the lower portion. In some embodiments, the at least one extension is substantially spherical or elliptical in shape. In some embodiments, the at least one extension has a triangular or polygonal shape (when viewed perpendicular to or along the vertical axis). In some embodiments, the internal cross-sectional area of ​​the extension increases and then decreases in a direction along the vertical axis from the lower portion to the upper portion. In some embodiments, there are at least two or at least three extensions. In some embodiments, the at least one extension creates a surface against which at least a portion of any liquid that evaporates may impinge, condense, and return to liquid at the lower portion of the liquid impinger. In some embodiments, the at least one extension creates a surface that inhibits evaporation. In some embodiments, the at least one extension creates a surface that inhibits evaporation and breaks up bubbles that flow toward the outlet. In some embodiments, at least one extension portion is immediately above (in the direction of the upper portion) and connected to the lower portion.

[0064]

[0078] In some embodiments, the liquid impinger further comprises at least one taper between the extension and the top, the at least one taper tapering along a vertical axis to a smaller internal cross-sectional area toward the top. In some embodiments, there are at least two or at least three tapers. In some embodiments, the at least one taper creates a surface against which at least a portion of any liquid that evaporates may impinge, condense, and return to liquid at the bottom of the liquid impinger. In some embodiments, the at least one taper creates a surface that inhibits evaporation. In some embodiments, the at least one taper creates a surface that inhibits evaporation and breaks up any air bubbles that flow toward the outlet. In some embodiments, the at least one taper is directly above (in the direction of the top) and connected to the at least one extension or substantially straight wall feature. In some embodiments, the taper tapers gradually, while in some embodiments, it tapers rapidly or abruptly.

[0065]

[0079] In some embodiments, the liquid impinger further comprises at least one substantially straight wall component between the extension and the tapered portion. For example, the substantially straight wall component is substantially straight with respect to the vertical axis. In some embodiments, the at least one substantially straight wall component is substantially cylindrical. In some embodiments, there are at least two or at least three substantially straight wall components (e.g., along the length of the vertical axis). In some embodiments, the at least one tapered portion is directly above (in the direction of the top) and connected to the at least one extension or substantially straight wall component. In some embodiments, the maximum widening point of the substantially straight wall component has an internal cross-sectional area that is smaller (or larger) than the cross-sectional area of ​​the maximum widening point at the bottom.

[0066]

[0080] In some embodiments, the liquid impinger further comprises a shelf or roof. In some embodiments, the shelf or roof includes a surface perpendicular to the vertical axis along with one or more openings that allow for the passage of gas. In some embodiments, the shelf or roof is located at a transition between portions of the liquid impinger that have different cross-sectional areas. In some embodiments, the shelf or roof divides the liquid impinger into one or more segments, where two segments have the same or different cross-sectional areas. In some embodiments, the shelf or roof is present at a transition point between an extension and a substantially straight wall configuration.

[0067]

[0081] In some embodiments, the liquid impinger comprises, in order, a lower portion comprising a cylindrical wall extending along at least a portion of a substantially vertical axis, an extension portion (e.g., substantially spherical or elliptical), a substantially straight wall configuration, and a tapered portion. In some embodiments, the liquid impinger comprises, in order, a lower portion comprising a cylindrical wall extending along at least a portion of a substantially vertical axis, an extension portion (e.g., substantially spherical or elliptical), and a tapered portion. In some embodiments, the liquid impinger comprises, in order, a lower portion comprising a substantially spherical or elliptical shape, an extension portion (e.g., substantially spherical or elliptical), a substantially straight wall configuration, and a tapered portion. In some embodiments, the liquid impinger comprises, in order, a lower portion comprising a substantially spherical or elliptical shape, an extension portion (e.g., substantially spherical or elliptical), and a tapered portion.

[0068]

[0082] In some embodiments, the liquid impinger is configured to operate with any suitable volume of liquid. In some embodiments, the liquid impinger is configured to operate with a volume (mL) of liquid of 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, or 200. Each of the above values ​​may be preceded or followed by the words "about," "at least," "at least about," "less than," or "less than about," and any of the above values ​​may be used alone to represent a single point or open-ended range or in combination to represent multiple single points or closed-ended ranges. For example, in some embodiments, the volume (mL) is 30-200, less than 150, 20-100, 20-150, 25-120, or 15-200.

[0069]

[0083] In some embodiments, the liquid impinger contains any suitable volume of liquid, in some embodiments, the volume of liquid (mL) is 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, or 200. Each of the above values ​​may be preceded or followed by the words "about," "at least," "at least about," "less than," or "less than about," and any of the above values ​​may be used alone to represent a single point or open-ended range or in combination to represent multiple single points or closed-ended ranges. For example, in some embodiments, the volume (mL) is 30-200, less than 110, 60-80, 20-150, 25-120, 15-200, 30-100, or less than 180.

[0070]

[0084] In some embodiments, the liquid impinger is filled with liquid to any suitable level. For example, in some embodiments, the liquid fills at least a portion of the lower portion. In some embodiments, the liquid fills the lower portion to within 1 cm of the top of the lower portion (e.g., the bottom of the extension, if present). In some embodiments, the liquid fills the entire lower portion. In some embodiments, the liquid impinger comprises, in order, a lower portion having a cylindrical wall extending along at least a portion of a substantially vertical axis, and an extension, and includes liquid that fills the entire lower portion but does not fill any portion of the extension (in some embodiments, the liquid fills the entire lower portion and at least a portion of the extension).

[0071]

[0085] In some embodiments, the liquid impinger has any suitable height, i.e., the length along the vertical axis, not including any hoses or other attachments. In some embodiments, the height (in cm) is 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, or 50. Each of the above values ​​may be preceded or followed by the words "about," "at least," "at least about," "less than," or "less than about," and any of the above values ​​may be used alone to represent a single point or open-ended range or in combination to represent multiple single points or closed-ended ranges. For example, in some embodiments, the height (cm) is 5-20, 10-20, less than 30, 15-18, or 25-44.

[0072]

[0086] In some embodiments, the liquid impinger has any suitable width, i.e., the dimension perpendicular to the vertical axis and not including any hoses or other attachments. In some embodiments, the width (cm) is 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15. Each of the above values ​​may be preceded or followed by the words "about", "at least", "at least about", "less than", or "less than about", and any of the above values ​​may be used alone to represent a single point or open-ended range, or in combination to represent multiple single points or closed-ended ranges. For example, in some embodiments, the width (cm) is 3 to 8, less than 10, or 5 to 15. As used herein, width may refer to the width of the liquid impinger at the point of greatest widening of the liquid impinger (which may be, for example, the bottom, the extension, the straight walled component, the gas outlet, or the gas inlet), the extension (if present) or bottom, or the width at the gas outlet, as is clear from the context.

[0073]

[0087] In some embodiments, at least a portion of the liquid impinger is constructed of a material sufficiently transparent to radiation to allow for sterilization of the liquid (if present) and interior by irradiation. In some embodiments, the material is a polymeric material as described elsewhere herein. In some embodiments, the material is different from a polymeric material. In some embodiments, the radiation comprises beta radiation, gamma radiation, x-rays, electron beam radiation, or any combination thereof. In some embodiments, the radiation comprises beta radiation, gamma radiation, or a combination thereof. In some embodiments, the radiation comprises ionizing radiation. In some embodiments, the radiation comprises shortwave radiation. In some embodiments, the radiation comprises high intensity radiation. In some embodiments, the radiation comprises ionizing, shortwave, high intensity radiation, including beta radiation, gamma radiation, or a combination thereof.

[0074]

[0088] In some embodiments, the liquid impinger is configured to be disposable. In some embodiments, the liquid impinger is configured to be used once to monitor the gas flow and then discarded. In some embodiments, the liquid impinger is configured to be disposable by being constructed of a polymeric material and not of glass.

[0075]

[0089] In some embodiments, the liquid impinger includes a port for testing of the liquid impinger. In some embodiments, the liquid impinger does not include a port for testing of the liquid impinger.

[0076]

[0090] In some embodiments, the present disclosure provides: Providing a fluid impinger, the fluid impinger comprising: a vessel including a vertical axis, an upper portion, an interior portion containing a liquid, and a lower portion including an interior base; a gas inlet disposed within the interior and in fluid communication with the interior through at least one nozzle attached to the lower portion, the nozzle including a nozzle opening, the nozzle opening being submerged in the liquid; and a gas outlet in fluid communication with the interior; wherein the gas inlet, the at least one nozzle, the interior, and the gas outlet in turn define a gas flow path; transporting a gas containing a test substance along a gas flow path within a liquid; transferring at least a portion of the particles from the gas to the liquid, optionally wherein the analyte comprises a particle, a molecular analyte, or a combination thereof, and further optionally, in some embodiments, wherein the analyte comprises a biological particle; A method is disclosed that includes:

[0077]

[0091] In some embodiments, the liquid impingers employed in these methods are the same as those described elsewhere herein, and as a result, the disclosures described elsewhere herein regarding liquid impingers are equally applicable with respect to the liquid impingers employed in these methods.

[0078]

[0092] In some embodiments, the gas containing the particles, molecular analytes, or both, comprises any suitable composition. In some embodiments, the gas comprises, consists of, or consists essentially of a sample gas. In some embodiments, the sample gas typically contains particles, but in some embodiments, it is particle-free or substantially particle-free (e.g., undetectable by standard cleanroom particle detection techniques), especially when derived from a cleanroom environment operating under uncontaminated, ideal conditions where the atmosphere is particle-free or substantially particle-free. In some embodiments, the sample gas comprises a carrier gas or sample medium (e.g., air, process gas, nitrogen, argon, carbon dioxide, carbon monoxide, oxygen, or any combination thereof). In some embodiments, the sample gas comprises air present in the environment to be sampled, such as the air inside a cleanroom, an isolator, a restricted access barrier system (RABS), or a manufacturing facility (e.g., a semiconductor or pharmaceutical manufacturing facility). In some embodiments, the sample gas consists of air (including any particles) from the environment to be sampled. In some embodiments, the air in the environment is mixed with a carrier gas, such as additional air, process gas, nitrogen, argon, carbon dioxide, carbon monoxide, oxygen, or any combination thereof, before or during the transfer step of the above methods, in such cases the sample gas comprises air from the environment to be sampled in combination with the carrier gas, in some embodiments the sample gas does not comprise a carrier gas, but such sample gas consists of air (with particles) present in the environment to be sampled.

[0079]

[0093] In some embodiments, the liquid impinger comprises at least two components, and the method further comprises filling the container with liquid prior to the providing step, either before or after assembly of the at least two components. In some embodiments, the liquid impinger comprises at least two components, and the method further comprises filling the container with liquid after the providing step, either before or after assembly of the at least two components. In some embodiments, the liquid impinger is filled with liquid after being assembled from the at least two components. In some embodiments, the liquid impinger is assembled from the at least two components after being filled with liquid prior to assembly of the at least two components. The assembly can be performed as described elsewhere herein. In some embodiments, the assembly and filling (in any order) are performed prior to providing the liquid impinger to an end user. In some embodiments, the assembly is performed prior to providing the liquid impinger to an end user, and the end user fills the container with liquid. In some embodiments, the end user assembles and fills the liquid impinger.

[0080]

[0094] In some embodiments, the method further includes irradiating the assembled and / or filled liquid impinger with radiation prior to the transporting step to sterilize at least a portion of the interior and at least a portion of the liquid contained therein, where at least a portion of the liquid impinger is constructed of a material that is sufficiently transparent to radiation to permit sterilization. In some embodiments, the entirety of the liquid contained therein is sterilized. In some embodiments, the entirety of the liquid impinger is sterilized. In some embodiments, the entirety of the liquid impinger is constructed of such a transparent material. In some embodiments, at least a portion of the lower portion of the liquid impinger that contains the liquid is constructed of such a material (e.g., the sidewall of the lower portion is constructed of such a material). In some embodiments, the entire lower portion of the liquid impinger (e.g., including the internal base) is constructed of such a material. In some embodiments, the lower portion of the liquid impinger includes at least one window of such a material, e.g., in a sidewall. In some embodiments, the lower portion is not transparent to such radiation. For example, in some embodiments, the extension is sufficiently transparent to radiation to permit sterilization of at least a portion of the interior and at least a portion of the liquid contained therein.

[0081]

[0095] In some embodiments, at least a portion of the test substances include particles, molecular test substances, or combinations thereof. In some embodiments, at least a portion of the test substances include biological particles, optionally living biological particles. For example, in some embodiments, at least a portion of the test substances include viruses, spores, microorganisms, bacteria, fungi, archaea, protists, single-celled microorganisms, or any combination thereof.

[0082]

[0096] In some embodiments, the method includes, after the moving step, placing caps, stoppers, or other obstructions on the gas inlet and gas outlet to prevent exposure of the liquid to contaminants, such as particles, before or during the incubation and / or detection steps. For example, after gas is sampled from a clean room environment, placement of caps on the gas inlet and outlet prevents collection of contaminants outside of the sampling period (e.g., during transport of the impinger to a location for incubation and / or detection).

[0083]

[0097] In some aspects, the moving step is carried out for any suitable period of time. For example, in some embodiments, the moving step is performed for 10, 20, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, or 500 minutes. Each of the above numerical values ​​may be preceded or followed by the words "about," "at least," "at least about," "less than," or "less than about," and any of the above numerical values ​​may be used alone to represent a single point or open-ended range, or in combination to represent multiple single points or closed-ended ranges. For example, in some embodiments, the time (minutes) is 10 to 500, 10 to 200, 20 to 80, at least 10, at least 35, 30 to 90, less than 115, or 60 to 90.

[0084]

[0098] In some embodiments, the method further comprises, after the transferring step, culturing the liquid under conditions sufficient to promote growth of viable biological particles, the liquid comprising a growth medium. Suitable growth media are described elsewhere herein. In some embodiments, the conditions sufficient to promote growth of viable biological particles include increasing the temperature of the growth medium above room temperature (e.g., to a temperature (°C) of 25, 26, 28, 30, 32, 34, 36, 37, 38, 40, 42, 44, or 45). Each of the above values ​​may be preceded or followed by the words "about", "at least", "at least about", "less than", or "less than about", any of which may be used alone to represent a single point or open-ended range or in combination to represent multiple single points or closed-ended ranges. For example, in some embodiments, the temperature (°C) of the culture is at least 25, 26-38, 30-42, or at least 30.

[0085]

[0099] In some embodiments, the culturing is carried out for any suitable period of time. For example, in some embodiments, the culturing time (in minutes) is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 40, 50, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 250, 300, 350, 400, 450, or 50. 0, or time (hours) is 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, 22, 24, 30, 36, 42, 48, 50, 55, 60, 65, 70, 72, 75, 80, 85, 90, 95, 100, 105, 110, 115, or 120. Each of the above values ​​may be preceded or followed by the words "about," "at least," "at least about," "less than," or "less than about," and any of the above values ​​may be used alone to represent a single point or open-ended range or in combination to represent multiple single points or closed-ended ranges. For example, in some embodiments, the incubation time is between 2 minutes and 120 hours, between 2 minutes and 30 minutes, between 30 minutes and 12 hours, at least 4 hours, less than 48 hours, between 24 hours and 120 hours, between 36 hours and 100 hours, or between 24 hours and 48 hours. In some embodiments, the incubation time is generally determined by the technique used for the analysis.

[0086]

[0100] In some embodiments, the method further comprises detecting whether contaminants, such as live biological particles, are present in the liquid. In some embodiments, the detecting comprises at least one of: (1) optical detection, including at least one of visual inspection by eye, the use of an optical detector, an imaging device, ultraviolet-visible, near-infrared, infrared, or fluorescence spectroscopy; (2) recognizing a change in oxygen or carbon dioxide levels in the liquid; or (3) analyzing the liquid after extraction from the liquid impinger using laboratory techniques, optionally including PCR. In some embodiments, the detecting comprises optical detection. In some embodiments, the detecting comprises recognizing a change in oxygen levels, carbon dioxide levels, or both. For example, recognizing a change in oxygen levels, carbon dioxide levels, or both comprises detecting such gases dissolved in or released from the liquid, or detecting such gases by indicator chemicals added to the liquid (e.g., titration). In some embodiments, the detecting comprises analyzing the liquid after extraction from the liquid impinger using laboratory techniques. In some embodiments, such laboratory techniques include polymerase chain reaction (PCR), nucleotide sequencing, hybridization (e.g., gene probes), restriction fragment length polymorphism (RFLP) analysis, flow cytometry, fluorescent in-situ hybridization (FISH), immunological identification (e.g., enzyme-linked immunosorbent assay (ELISA)), fatty acid profiling, metabolic profiling, or any combination thereof.

[0087]

[0101] In some embodiments, at least one of the culturing or detecting steps is performed without removal of liquid from the container or disassembly of the liquid impinger. For example, in some embodiments, following the transferring step, the liquid remains in the liquid impinger throughout the culturing and detecting steps. In some embodiments, the liquid remains in the liquid impinger during culturing, but is removed from the liquid impinger or disassembled prior to the detecting step. In some embodiments, the liquid is removed from the liquid impinger prior to culturing, such that the culturing and detecting steps are performed with the liquid outside of the liquid impinger. In such embodiments where the liquid for culturing and / or detecting is outside of the liquid impinger, it is desirable to handle the liquid carefully to avoid contaminating the liquid with contaminants such as particles, and to detect only particles present in the liquid by the transferring step of the method.

[0088]

[0102] In some embodiments, the combined performance of the filling and sterilizing steps minimizes human contact with the liquid and reduces false positives in the detecting step. In some embodiments, not removing the liquid from the liquid impinger during the incubation and detecting steps also minimizes human contact with the liquid and reduces false positives. Thus, in some embodiments, minimizing human contact with the liquid and reducing false positives is accomplished prior to the providing step by filling the container with liquid prior to the transport step, irradiating the assembled and / or filled liquid impinger to sterilize at least a portion of the interior and at least a portion of the liquid contained therein, and performing the transferring step followed by performing the incubation and detecting steps (without removing the liquid from the container).

[0089]

[0103] In some embodiments, the liquid impinger is configured for disposable use. In some embodiments, the method further comprises at least one of the following steps after performing one cycle of the preparing, transporting, transferring, incubating, and detecting steps: (1) discarding the liquid impinger; (2) not sterilizing the liquid impinger again in preparation for a second cycle of the preparing, transporting, transferring, incubating, and detecting steps; or (3) not performing a second cycle of the preparing, transporting, transferring, incubating, and detecting steps again. In some embodiments, the method further comprises discarding the liquid impinger after performing one cycle of the preparing, transporting, transferring, incubating, and detecting steps. In some embodiments, the method further comprises not sterilizing the liquid impinger with radiation sufficient to sterilize any liquid within the liquid impinger after performing one cycle of the preparing, transporting, transferring, incubating, and detecting steps. In some embodiments, the method further comprises, after performing one cycle of the providing, transporting, transferring, culturing, and detecting steps, not performing a second cycle of the providing, transporting, transferring, culturing, and detecting steps.

[0090]

[0104] As described elsewhere herein, in some embodiments, the liquid impinger employed in these methods is the same as the liquid impinger described elsewhere herein. As a result, the disclosures described elsewhere herein regarding liquid impingers are equally applicable to the liquid impingers employed in these methods. For example, in some embodiments of the above methods, the at least one nozzle includes at least two nozzles or at least three nozzles. In some embodiments of the above methods, each nozzle opening has a diameter of 0.1 mm to 3.2 mm. In some embodiments of the above methods, the at least one nozzle includes a shape including a circular arc, the arc being substantially in a plane that forms an angle of 85° to 95° with a vertical axis. In some embodiments of the above methods, the at least one nozzle has a horizontal angle of 0° to 40°. In some embodiments of the above methods, the gas inlet is connected to the at least one nozzle by a tube extending from the top to the bottom inside. In some embodiments of the above method, the lower portion comprises a cylindrical, spherical, or elliptical shape, and the liquid impinger further comprises at least one extension between the lower portion and the upper portion, the extension having a greater internal cross-sectional area at a maximum widening point than the internal cross-sectional area at the maximum widening point of the lower portion, and at least one tapered portion between the extension and the upper portion, the at least one tapered portion tapering along a vertical axis to a smaller internal cross-sectional area toward the upper portion. In some embodiments of the above method, the lower portion further comprises a sidewall, and the nozzle opening is disposed within 10 mm of the sidewall or substantially flush with the sidewall. In some embodiments, the liquid impinger comprises a polymeric material. In some embodiments, the polymeric material comprises poly(acrylonitrile-butadiene-styrene), polyethylene, polycarbonate, polyamide, polystyrene, clear polystyrene (e.g., Polystyrol™ available from BASF), high impact polystyrene, polypropylene, polyoxymethylene, polyurethane, rubber, or any combination thereof.

[0091]

[0105] In some embodiments, the conveying step is performed at any suitable flow rate. For example, in some embodiments, the flow rate (L / min) into the gas inlet and / or out of the gas outlet is 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 19.5, or 20. Each of the above values ​​may be preceded or followed by the words "about," "at least," "at least about," "less than," or "less than about," and any of the above values ​​may be used alone to represent a single point or open-ended range or in combination to represent multiple single points or closed-ended ranges. For example, in some embodiments, the flow rate (L / min) into the gas inlet and / or out of the gas outlet is 1-20, 1-4, 3-5, at least 2, at least 3.5, less than 8, 5.5-18, 10-20, 8-15, or 3.5-9.

[0092]

[0106] In some embodiments, the velocity of the gas flowing out of the nozzle is any suitable velocity. For example, in some embodiments, the velocity (m / s) of the gas flowing out of the nozzle is 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, or 120. Each of the above values ​​can be preceded or followed by the words "about", "at least", "at least about", "less than", or "less than about", and any of the above values ​​can be used alone to represent a single point or open-ended range, or in combination to represent multiple single points or closed-ended ranges. For example, in some embodiments, the velocity (m / s) of the gas flowing out of the nozzle is 10 to 120, 70 to 80, less than 80, less than 85, at least 40, 45 to 120, 80 to 110, or 50 to 85. In some embodiments, when two or more nozzles are employed in the liquid impinger, each nozzle independently has any of the velocities disclosed herein. In some embodiments, when two or more nozzles are employed in the liquid impinger, each nozzle has the same velocity selected from any of the velocities disclosed. In some embodiments, the velocity is selected to maintain the viability (e.g., not kill or disable) of microorganisms, viruses, or other biological particles that may be present. In some embodiments, the velocity is selected to promote swirling of the liquid within the lower portion. For example, in some embodiments, the velocity is selected to promote swirling of the liquid within the lower portion, thereby increasing (e.g., maximizing) bubble residence time in the gas and improving bubble-to-liquid transfer.

[0093]

[0107] In some embodiments, a method for generating a liquid impinger includes the steps of: forming at least two components of a liquid impinger; Optionally, creating an assembled liquid impinger by assembling at least two components, the assembled liquid impinger comprising: a vessel including a vertical axis, an upper portion, an interior portion, and a lower portion including an interior base; a gas inlet disposed within the interior and in fluid communication with the interior through at least one nozzle attached to the lower portion, the nozzle including a nozzle opening; and a gas outlet in fluid communication with the interior; Equipped with the gas inlet, the at least one nozzle, the interior, and the gas outlet, in turn, define a gas flow path; a container configured to contain a liquid therein; Optionally, filling a portion of the interior of the assembled liquid impinger with liquid to create a filled liquid impinger; Optionally, exposing the filled liquid impinger to radiation to sterilize at least a portion of the liquid present within the liquid impinger, thereby producing a filled and sterile liquid impinger; Optionally, either before or after the exposing step, packaging the filled liquid impinger or the filled and sterile liquid impinger in a manner that prevents ingress of particles or contamination into the interior of the liquid impinger; A method is disclosed that includes:

[0094]

[0108] In some embodiments, a method for producing a filling and sterilizing liquid impinger includes the steps of: forming at least two components of a liquid impinger; creating an assembled liquid impinger by assembling at least two components, the assembled liquid impinger comprising: a vessel including a vertical axis, an upper portion, an interior portion, and a lower portion including an interior base; a gas inlet disposed within the interior and in fluid communication with the interior through at least one nozzle attached to the lower portion, the nozzle including a nozzle opening; and a gas outlet in fluid communication with the interior; Equipped with the gas inlet, the at least one nozzle, the interior, and the gas outlet, in turn, define a gas flow path; a container configured to contain a liquid therein; filling a portion of an interior of the assembled liquid impinger with liquid to create a filled liquid impinger; exposing the filled liquid impinger to radiation to sterilize at least a portion of the liquid present within the liquid impinger, thereby producing a filled and sterile liquid impinger; Optionally, either before or after the exposing step, packaging the filled liquid impinger or the filled and sterile liquid impinger in a manner that prevents ingress of particles or contamination into the interior of the liquid impinger; A method is disclosed that includes:

[0095]

[0109] In some embodiments, a method for producing a filling and sterilizing liquid impinger includes the steps of: A first providing step includes providing a filled liquid impinger, the filled liquid impinger comprising: a vessel including a vertical axis, an upper portion, an interior portion, and a lower portion including an interior base; a gas inlet disposed within the interior and in fluid communication with the interior through at least one nozzle attached to the lower portion, the nozzle including a nozzle opening; and a gas outlet in fluid communication with the interior; Equipped with the gas inlet, the at least one nozzle, the interior, and the gas outlet, in turn, define a gas flow path; a container containing a liquid therein; exposing the filled liquid impinger to radiation to sterilize at least a portion of the liquid present within the liquid impinger, thereby producing a filled and sterile liquid impinger; Optionally, either before or after the exposing step, packaging the filled liquid impinger or the filled and sterile liquid impinger in a manner that prevents ingress of particles or contamination into the interior of the liquid impinger; A method is disclosed that includes:

[0096]

[0110] In some embodiments, the liquid impinger employed in the method for producing the liquid impinger or the filled and sterilized liquid impinger is the same as the liquid impinger described elsewhere herein. As a result, the disclosures elsewhere herein regarding the liquid impinger are equally applicable to the liquid impinger employed in such a method. Also, various aspects of the method steps described elsewhere herein for the use of the liquid impinger are applicable to the method for producing the liquid impinger or the filled and sterilized liquid impinger. For example, the filling, irradiating / sterilizing / exposing, and cap / stopper placement steps are equally applicable here, while any method or method steps described elsewhere herein for the method of constructing are applicable.

[0097]

[0111] In some aspects, any method step may or may not be performed, including any steps that may or may not be specified as optional. For example, in some aspects, an assembling step is performed. In some aspects, a filling step is performed. In some aspects, an exposing step is performed. In some aspects, a packaging step is performed. In some aspects, any combination of these steps is performed. For example, in some aspects, a forming step and an assembling step are performed. In some aspects, forming, assembling, and filling are performed. In some aspects, a filling step and an exposing step are performed. In some aspects, assembling, filling, and exposing steps are performed. In some aspects, forming, assembling, filling, and exposing steps are performed. In some aspects, the forming step is optional. In some aspects, a forming step is not performed and a assembling step is performed. In some aspects, a forming step is not performed and a forming step is performed. In some aspects, a forming step is not performed and a forming step is performed. In some aspects, a forming step is not performed and a forming step is performed. In some aspects, a forming step is not performed and a forming step is performed. In some aspects, a forming step is not performed and a forming step is performed. In some aspects, a forming step is not performed and a forming step is performed. In some aspects, the forming step is not performed and the filling and exposing steps are performed.

[0098]

[0112] In some embodiments, the assembling step is performed by attaching or connecting the various components of the liquid impinger in any suitable manner. It is useful to understand one embodiment of the assembling step by referring to FIG. 12, which shows a three-component liquid impinger including components 1201, 1202, and 1203 shown in outline. For example, in some embodiments, component 1201 is attached to component 1202 via two attachment points at 1204, where a smaller diameter tube of component 1201 abuts or wedges into a larger diameter tube of component 1202, and at 1205, where components 1201 and 1202 are screwed together. In some embodiments, component 1202 has a smaller diameter tube that abuts or wedges into the larger diameter tube of component 1201. In some embodiments, such connections at 1204 and 1205 may be held together independently in any suitable manner, for example, by friction, adhesive, heat melt, threading, or any combination thereof. In FIG. 12, component 1203 is attached to component 1202, however, the components may be held together in any suitable manner, for example, by friction, adhesive, heat melt, threading, or any combination thereof.

[0099]

[0113] In some embodiments, the filling step may be performed in any suitable manner. For example, in some embodiments, the filling step is performed by adding liquid to the interior of the liquid impinger through the top, e.g., by an outlet. In some embodiments, the filling step is performed in a liquid impinger in which a component comprising a lower portion (e.g., component 1202 in FIG. 12 ) is separate from a component comprising an upper portion (e.g., component 1201 in FIG. 12 ). In such embodiments, the filling step includes filling the lower portion with liquid to a desired level and then assembling the components comprising the upper and lower portions (e.g., by screwing). In some embodiments, the filling is performed by a pipette.

[0100]

[0114] In some embodiments, the method further comprises, prior to the first providing step: a second providing step including providing an assembled liquid impinger, the assembled liquid impinger including a filled liquid impinger without liquid; filling a portion of an interior of the assembled liquid impinger with liquid to create a filled liquid impinger; Further includes:

[0101]

[0115] In some aspects, the assembled liquid impinger is fully or partially assembled and the filling step is performed on the fully or partially assembled liquid impinger. In some aspects, the fully or partially assembled liquid impinger is configured to contain liquid therein. In some aspects, if the assembled liquid impinger is a partially assembled liquid impinger, the filling step is performed before the partially assembled liquid impinger is fully assembled. In some aspects, if the assembled liquid impinger is a partially assembled liquid impinger, the filling step is performed before the partially assembled liquid impinger is fully assembled and then the exposing step is performed on the fully assembled liquid impinger. In some aspects, if the assembled liquid impinger is a partially assembled liquid impinger, the filling step is performed before the exposing step is performed on the filled partially assembled liquid impinger and then the partially assembled liquid impinger is fully assembled.

[0102]

[0116] In some embodiments, the method further comprises, prior to the second providing step, creating an assembled liquid impinger by assembling at least two components, hi some embodiments, the at least two components comprise three components, four components, five components, six components, or seven components.

[0103]

[0117] In some embodiments, the method further comprises forming the at least two components prior to the assembling step, hi some embodiments, the forming step comprises molding, injection molding, blow molding, rotational molding, additive manufacturing, three-dimensional printing, subtractive manufacturing, casting, molding, vacuum forming, extrusion, or any combination thereof.

[0104]

[0118] In some embodiments, the forming step forms one or more polymeric materials into at least two components. In some embodiments, the one or more polymeric materials include poly(acrylonitrile-butadiene-styrene), polyethylene, polycarbonate, polyamide, polystyrene, clear polystyrene (e.g., Polystyrol™ available from BASF), high impact polystyrene, polypropylene, polyoxymethylene, polyurethane, rubber, or any combination thereof. Other suitable polymeric materials are described elsewhere herein.

[0105]

[0119] In some embodiments, the radiation comprises beta rays, gamma rays, X-rays, electron beam rays, or any combination thereof.

[0106]

[0120] In some embodiments, the liquid comprises a growth medium.

[0107]

[0121] In some embodiments, the method further comprises the step of irradiating the at least two components, the assembled liquid impinger, or both, with radiation prior to the filling step to sterilize, the radiation comprising beta radiation, gamma radiation, x-rays, electron beam radiation, or any combination thereof. Such radiation can be the same as or different from the exposing step. In some embodiments, the method can use radiation before, during, or after any step to sterilize at least a portion of the interior, any components making up at least a portion of the interior, any liquid contained within, or any combination thereof.

[0108]

[0122] In some embodiments, the filled liquid impinger or the filled and sterile liquid impinger is packaged to prevent ingress of particles or contamination into the interior of the liquid impinger, either before or after the exposing step. In some embodiments, the packaging step is performed before the exposing step. In some embodiments, the packaging step is performed after the exposing step. In some embodiments, the packaging step is performed and includes (1) attaching caps to one or more gas inlets and gas outlets, (2) sealing the filled liquid impinger or the filled and sterile liquid impinger in a container, or (3) a combination thereof. In some embodiments, the container is a bag (e.g., a plastic bag). In some embodiments, the container (e.g., a bag) is impermeable or semi-permeable to particles having a size range that the method using the liquid impinger is configured to detect, so as to effectively prevent ingress of such particles or contamination into the liquid impinger and avoid false positives. In some embodiments, the packaging step includes sealing the liquid impinger in one layer of packaging (e.g., a container or bag). In some embodiments, the packaging step includes enclosing the liquid impinger in at least two layers of packaging to allow for proper handling, for example, upon entry into a clean room or other sterile zone. Any suitable packaging material may be used. For example, in some embodiments, plastics such as polypropylene or polyethylene may be used as packaging materials.

[0109]

[0123] Aspects of the present invention may be further understood by the following non-limiting drawings.

[0110]

[0124] 1 illustrates several embodiments of a liquid impinger, particularly a liquid impinger for sampling gas. The liquid impinger 100 includes a vertical axis 101, a top portion 102, a bottom portion 103, a gas inlet 104, a gas outlet 105, an interior 106, an interior base 107, a nozzle 108, a nozzle opening 109, a tube 110, and a sidewall 113. The bottom portion 103 includes the interior base 107. The gas inlet 104 is disposed in the interior 106 and is in fluid communication with the interior 106 through a nozzle 108 that is attached to the bottom portion 103. The nozzle 108 is shown attached to the interior base 107, but can be attached or positioned anywhere within the bottom portion 103 (e.g., can be attached to the sidewall 113). The gas inlet 104 is connected to the nozzle 108 by a tube 110 that extends from the top portion 102 to the bottom portion 103 in the interior 106. The gas outlet 105 is in fluid communication with the interior 106. The gas inlet 104, the nozzle 108, the interior 106, and the gas outlet 105 sequentially define a gas flow path. The gas flow path is bent at an angle of 80° to 100° between the tube 110 and the nozzle 108. The lower portion 103 includes a wall, which may be cylindrical, extending substantially along at least a portion of the vertical axis 101. The gas outlet 105 is located in the upper portion 102. The liquid impinger 100 does not include an extension, a taper, or a liquid.

[0111]

[0125] FIG. 2 illustrates several embodiments of liquid impingers, particularly liquid impingers for sampling gas. The liquid impinger 200 of FIG. 2 is similar to the liquid impinger 100 of FIG. 1, except that a tube supplying gas is approached from the bottom of the liquid impinger, rather than a tube running through the interior. The liquid impinger 200 includes a vertical axis 201, an upper portion 202, a lower portion 203, a gas inlet 204, a gas outlet 205, an interior 206, an interior base 207, a nozzle 208, a nozzle opening 209, a tube 211, and a sidewall 213. The lower portion 203 includes an interior base 207. The gas inlet 204 is disposed in the interior 206 and is in fluid communication with the interior 206 via a nozzle 208 that is attached to the lower portion 203. Although the nozzle 208 is shown attached to the interior base 207, it can be attached or positioned anywhere within the lower portion 203 (e.g., it can be attached to the sidewall 213). The gas inlet 204 is connected to the nozzle 208 by a tube 211 approaching the lower portion 103 from below the liquid impinger 200. The gas outlet 205 is in fluid communication with the interior 206. The gas inlet 204, the nozzle 208, the interior 206, and the gas outlet 205 sequentially define a gas flow path. The gas flow path is bent at an angle of 80° to 100° between the tube 210 and the nozzle 208. The lower portion 203 includes a wall extending substantially along at least a portion of the vertical axis 201, which may be cylindrical. The gas outlet 205 is located in the upper portion 202. The liquid impinger 200 does not include an extension, a taper, or a liquid.

[0112]

[0126] Figure 3 illustrates several embodiments of liquid impingers, particularly liquid impingers for sampling gas. The liquid impinger 300 of Figure 3 is similar to the liquid impinger 100 of Figure 1, except that it additionally includes, for example, a liquid, an extension, and a tapered portion. The liquid impinger 300 includes a vertical axis 301, an upper portion 302, a lower portion 303, a gas inlet 304, a gas outlet 305, an interior 306, an interior base 307, a nozzle 308, a nozzle opening 309, a tube 310, a liquid 312, a sidewall 313, an extension 314, a tapered portion 315, and a substantially straight wall configuration 316. The lower portion 303 includes an interior base 307. The gas inlet 304 is disposed in the interior 306 and is in fluid communication with the interior 306 via a nozzle 308 attached to the lower portion 303. Nozzle 308 is shown attached to interior base 307, but may be attached or positioned anywhere within lower portion 303 (e.g., attached to sidewall 313). Gas inlet 304 is connected to nozzle 308 by tube 310 that extends from upper portion 302 to lower portion 303 in interior 306. Gas outlet 305 is in fluid communication with interior 306. Gas inlet 304, nozzle 308, interior 306, and gas outlet 305 sequentially define a gas flow path. The gas flow path is bent at an angle of 80°-100° between tube 310 and nozzle 308. Nozzle 308 is immersed in liquid 312 and conveys gas along the gas flow path, causing the gas to pass through liquid 312. Liquid 312 fills the lower portion close to the point where the lower portion joins the extension (although in some embodiments the liquid may fill the entire lower portion and in some embodiments a portion of the extension, or may fill a smaller area of ​​the lower portion). The lower portion 303 comprises a wall that extends substantially along at least a portion of the vertical axis 301, which wall may be cylindrical. The liquid impinger 300 comprises, in order, the lower portion 303, the extension portion 314 (which may be substantially spherical or elliptical), a substantially straight wall configuration 316, and a tapered portion 315. The tapered portion 315 has a relatively rapid or sharp taper. A gas outlet 305 is disposed in the upper portion 302.In operation, gas enters gas inlet 304, passes along tube 310 through nozzle 308, exits nozzle opening 309, passes through liquid 312, passes through interior 306 via expansion 314, substantially straight wall configuration 316, tapered section 315, and exits through gas outlet 305. In some embodiments, conveying gas through the liquid impinger causes swirling of liquid 312 in lower portion 303.

[0113]

[0127] Figure 4 illustrates several embodiments of liquid impingers, particularly liquid impingers for sampling gas. The liquid impinger 400 of Figure 4 is similar to the liquid impinger 300 of Figure 3, except that, for example, the extension of the liquid impinger 400 differs in some respects. The liquid impinger 400 includes a vertical axis 401, an upper portion 402, a lower portion 403, a gas inlet 404, a gas outlet 405, an interior 406, an interior base 407, a nozzle 408, a nozzle opening 409, a tube 410, a sidewall 413, an extension 414, a tapered portion 415, and a substantially straight wall configuration 416. The lower portion 403 includes an interior base 407. The gas inlet 404 is disposed in the interior 406 and is in fluid communication with the interior 406 via a nozzle 408 attached to the lower portion 403. Nozzle 408 is shown attached to interior base 407, but may be attached or positioned anywhere within lower portion 403 (e.g., attached to sidewall 413). Gas inlet 404 is connected to nozzle 408 by tube 410, which extends from upper portion 402 to lower portion 403 at interior 406. Gas outlet 405 is in fluid communication with interior 406. Gas inlet 404, nozzle 408, interior 406, and gas outlet 405, in turn, define a gas flow path. The gas flow path is bent at an angle of 80°-100° between tube 410 and nozzle 408. Although no liquid is shown, if liquid is present, nozzle 408 would be immersed in the liquid and convey the gas along the gas flow path, causing the gas to pass through the liquid. Lower portion 403 includes a wall extending substantially along at least a portion of vertical axis 401, which may be cylindrical. The liquid impinger 400 comprises, in order, a lower portion 403, an extension 414 (triangular shaped), a substantially straight walled portion 416, and a tapered portion 415. The tapered portion 415 has a relatively gradual taper. A gas outlet 405 is disposed in the upper portion 402. In operation, gas enters the gas inlet 404, passes along the tube 410 through the nozzle 408, exits the nozzle opening 409, passes through the liquid (if present), passes through the extension 414, the substantially straight walled portion 416, the tapered portion 415, passes through the interior 406, and exits through the gas outlet 405.In some embodiments, conveying gas through the liquid impinger causes swirling of liquid (if present) in lower portion 403 .

[0114]

[0128] FIG. 5 illustrates several embodiments of liquid impingers, particularly liquid impingers for sampling gas. The liquid impinger 500 of FIG. 5 is similar to the liquid impinger 300 of FIG. 3 and the liquid impinger 400 of FIG. 4, except that, for example, the shape of the lower portion of the liquid impinger 500 is different. All features of FIG. 5 that are not specifically specified are the same as FIG. 3 and FIG. 4. The liquid impinger 500 includes a vertical axis 501, an upper portion 502, a tapered portion 515, a substantially straight walled portion 516, a lower portion 503, and an internal base 507. The lower portion 503 includes a spherical or elliptical shape. The internal base 507 is shown as being flat, but may have any suitable shape, such as spherical, concave, or convex, as described elsewhere herein. Operation of the liquid impinger 500 according to the methods disclosed herein is similar to that described in other figures herein, such as FIG. 3 and FIG. 4.

[0115]

[0129] 6A-6D show several embodiments of liquid impingers. For example, 6A-6D show various nozzle configurations in the lower part of the liquid impinger. 6A shows a configuration of the lower part of the liquid impinger where the nozzles are supplied with gas flow via tubes attached to the sidewall of the lower part. The nozzle direction is perpendicular to the plane of the figure. 6B shows a configuration of the lower part of the liquid impinger where the two nozzles are supplied with gas flow via tubes approaching the lower part from below, and the internal base of the lower part is concave, spherical, or elliptical. The nozzle direction is perpendicular to the plane of the figure or angled upward toward the sidewall. 6C shows a configuration of the lower part of the liquid impinger where the two nozzles are supplied with gas flow via tubes located inside the liquid impinger, and the nozzles are attached to the internal base and optionally the sidewall. The nozzle direction is perpendicular to the plane of the figure. 6D shows the configuration of the lower part of the liquid impinger where the gas flow is fed to two nozzles via tubes located inside the liquid impinger, and the nozzles are optionally mounted on an internal base, with the nozzles oriented perpendicular to the plane of the page or angled towards (but not perpendicular to) the sidewall.

[0116]

[0130] 7A and 7B show aspects of nozzle configurations. In particular, FIGS. 7A and 7B show the lower interior base 709 of the liquid impinger as viewed from the top along the vertical axis. There are three nozzles 708 in each view, each with a nozzle opening 709 and including a shape that includes a circular arc. The arc lies substantially in a plane that forms an angle of 85° to 95° with the vertical axis. Feature 721 identifies the location where the tube that delivers the gas flow from the gas inlet is located. Other features of FIGS. 7A and 7B are described elsewhere herein to aid in understanding the definition of the term "horizontal angle."

[0117]

[0131] FIG. 8 is referenced elsewhere in this specification to aid in understanding the definition of the term "vertical angle."

[0118]

[0132] 9 illustrates several embodiments of liquid impingers, particularly liquid impingers for sampling gas. The liquid impinger 900 includes a vertical axis 901, a top portion 902, a bottom portion 903, a gas inlet 904, a gas outlet 905, an interior 906, an interior base 907, a nozzle 908, a nozzle opening 909, a tube 910, a sidewall 913, an extension 914, a tapered portion 915, and three substantially straight wall configurations 916. The bottom portion 903 includes an interior base 907. The gas inlet 904 is disposed in the interior 906 and is in fluid communication with the interior 906 through a nozzle 908 attached to the bottom portion 903. The gas inlet 904 is connected to the nozzle 908 by a tube 910 that extends from the top portion 902 to the bottom portion 903 in the interior 906. The gas outlet 905 is in fluid communication with the interior 906. A gas flow path is sequentially defined by the gas inlet 904, the nozzle 908, the interior 906, and the gas outlet 905. The gas flow path is bent at an angle of 80° to 100° between the tube 910 and the nozzle 908. Although liquid is not shown, if liquid is present, the nozzle 908 is immersed in the liquid and conveys the gas along the gas flow path, causing the gas to pass through the liquid. The lower portion 903 includes a wall that extends substantially along at least a portion of the vertical axis 901, which may be cylindrical. The liquid impinger 900 includes, in order, the lower portion 903, an extension 914 (substantially spherical or elliptical), a substantially straight wall component 916, a shelf 924 that allows a transition to the substantially straight wall component 916 having a smaller cross-sectional area, a tapered portion 915, and another substantially straight wall component 916. The tapered portion 915 has a relatively rapid or steep taper. Gas outlet 905 is located in top 902. In operation, gas enters gas inlet 904, passes along tube 910 through nozzle 908, exits nozzle opening 909, passes through liquid (not shown), through interior 906 and out gas outlet 905. In some embodiments, conveying gas through the liquid impinger causes a swirling of the liquid (not shown) in bottom 903. Feature 923 denotes threads that, in this embodiment, allow for assembly and disassembly of the liquid impinger by rotation along these threads. Feature 922 is an optional port for testing the liquid impinger.

[0119]

[0133] Figure 10 is an exterior view of the liquid impinger of Figure 9. Liquid impinger 1000 includes a vertical axis 1001, a top portion 1002, a bottom portion 1003, a gas inlet 1004, a gas outlet 1005, a sidewall 1013, an extension 1014, a tapered portion 1015, and three substantially straight wall sections 1016. Feature 1022 is an optional port for testing the liquid impinger.

[0120]

[0134] Figures 13A and 13B are perspective views of a liquid impinger of the present invention showing an exemplary angular orientation of the gas inlets and tubes relative to the nozzles, and Figures 14A and 14B are top views showing an exemplary angular orientation of the nozzles of this liquid impinger.

[0121]

[0135] FIG. 11 is a flow diagram of some embodiments of a method for producing a liquid impinger or a method for producing a filled and sterile liquid impinger. Some embodiments of these methods include step 1101 of forming at least two components of a liquid impinger, step 1102 of assembling the at least two components to produce an assembled liquid impinger, step 1103 of filling a portion of the interior of the assembled liquid impinger with liquid to produce a filled liquid impinger, and step 1104 of exposing the filled liquid impinger to radiation to sterilize at least a portion of the liquid present in the interior of the liquid impinger to produce a filled and sterile liquid impinger. In some embodiments, the method further includes step 1105, which is performed either before or after the exposing step 1104, as shown in FIG. 11. In some embodiments, any of the steps shown in FIG. 11 may or may not be performed. For example, in some embodiments, all steps are performed and step 1105 is performed either before or after step 1104. In some embodiments, the forming step 1101 is not performed and the assembling step 1102 and the filling step 1103 are performed. In some embodiments, the forming step 1101 is not performed and the assembling step 1102, the filling step 1102, and the exposing step 1103 are performed. In some embodiments, the forming step 1101 and the assembling step 1102 are performed and the filling step 1103, the exposing step 1104, and the packaging step 1105 are not performed. In some embodiments, the forming step 1101, the assembling step 1102, the filling step 1103, and the exposing step 1104 are performed. All possible combinations of steps are contemplated and any step may be performed, may not be performed, or may be combined with any other step, whether performed or not.

[0122]

[0136] FIG. 12 is described elsewhere herein to aid in understanding how the various components of the liquid impinger are attached to one another, including how the liquid impinger is assembled.

[0123]

[0137] 15A-15C, which show one example of a liquid impinger 1300. The liquid impinger 1300 includes a sample port 1360 and a cap 1350. The sample port 1360 is configured to provide selective access to a liquid contained within an interior of a container. The cap 1350 includes a septum 1355. The septum 1355 can be constructed of rubber or a similar material that allows for the penetration of a needle while maintaining a barrier between the interior of the impinger and the surrounding environment.

[0124]

[0138] In some embodiments, the impinger may be molded, assembled, filled with a liquid medium, capped, sterilized, and then provided to an end user who may sample the gas stream with the liquid impinger and then extract a liquid sample by piercing the septum with a syringe. Thus, false positives can be reduced by the sealed sampling action facilitated by the sampling port and septum.

[0125] (Example)

[0139] Aspects of the present invention can be further understood by the following non-limiting examples.

[0126]

[0140] Example 1: Liquid Impinger

[0127]

[0141] The present examples illustrate several aspects of a fluid impinger, particularly a disposable fluid impinger that is used once and then discarded.

[0128]

[0142] A disposable impinger has the following components / features: (1) an ampoule in which the liquid medium resides, (2) an inlet cannula that expands air into the liquid, (3) a vacuum connection, (4) a cap for the vacuum connection, (5) a cap for the inlet cannula, and (6) all materials constructed of plastic (e.g., polymeric material).

[0129]

[0143] The steps for producing and using a liquid impinger include (1) constructing the components by molding, (2) sterilizing by beta irradiation, (3) filling ampoules with media and assembling the device, (4) sterilizing by gamma irradiation, (5) shipping to the customer, (6) placement at the sampling point, connecting the vacuum source and inlet probe, (7) sampling, applying vacuum, (8) removing the device from the sampling point, capping the inlet and vacuum connections, and (9) detecting bacteria in the liquid.

[0130]

[0144] The advantages of disposable liquid impingers are: (1) easier detection of bacteria in liquids with less handling; (2) minimal or no false positives due to sterilization of the disposable closed device; and (3) their special design minimizes liquid loss during sampling, thus extending monitoring time and minimizing size.

[0131]

[0145] The liquid impingers and methods disclosed herein solve many of the problems of known samplers. For example, practical general microbial detection in clean room environments is often performed using Petri dishes. While some solutions, such as disposable agar-filled Petri dishes, allow for non-contact media throughout growth / cultivation, the detection / recognition step is still manual and subject to contamination due to human manipulation / intervention. Also, the incubation / growth time in agar Petri dishes is several days (e.g., 2-3 days). However, in liquid media, incubation / growth can be faster, and there are several methods that allow for less handling in combination with detection techniques such as PCR. While liquid impingers can provide monitoring, known impingers are typically constructed of glass and are therefore not consumable (i.e., disposable). They must be cleaned and sterilized prior to each repeated use. Furthermore, known liquid impingers are often too large to allow ideal placement at the monitoring point.

[0132]

[0146] For example, Figures 3 and 9 show an embodiment of a disposable fluid impinger according to the present embodiment.

[0133]

[0147] Additional aspects include the following:

[0134]

[0148] Aspect 1. A vessel including a vertical axis, an upper portion, an interior portion, and a lower portion including an interior base; a gas inlet disposed within the interior and in fluid communication with the interior through at least one nozzle attached to the lower portion, the nozzle including a nozzle opening; and a gas outlet in fluid communication with the interior; Equipped with the gas inlet, the at least one nozzle, the interior, and the gas outlet, in turn, define a gas flow path; A liquid impinger, wherein the container is configured to contain a liquid therein.

[0135]

[0149] Embodiment 2. The liquid impinger of embodiment 1, wherein the liquid impinger comprises a polymeric material.

[0136]

[0150] Aspect 3. The liquid impinger of aspect 2, wherein the polymeric material comprises poly(acrylonitrile-butadiene-styrene), polyethylene, polycarbonate, polyamide, polystyrene, clear polystyrene (e.g., Polystyrol™), high impact polystyrene, polypropylene, polyoxymethylene, polyurethane, rubber, or any combination thereof.

[0137]

[0151] Aspect 4. A liquid impinger according to any one of Aspects 1-3, wherein when the liquid impinger contains a liquid, at least one nozzle is immersed in the liquid and conveys the gas along the gas flow path, thereby causing the gas to pass through the liquid.

[0138]

[0152] Embodiment 5. The liquid impinger of any one of embodiments 1 to 4, further comprising a liquid.

[0139]

[0153] Aspect 6. A liquid impinger according to any one of aspects 1-5, wherein the liquid impinger is produced by a process including molding, injection molding, blow molding, rotational molding, additive manufacturing, three dimensional printing, subtractive manufacturing, casting, molding, vacuum forming, extrusion, or any combination thereof, and optionally the process produces at least three separate components joined together to form the liquid impinger.

[0140]

[0154] Embodiment 7. The liquid impinger of any one of embodiments 1-6, wherein the at least one nozzle comprises at least two nozzles or at least three nozzles.

[0141]

[0155] Embodiment 8. A liquid impinger according to any one of embodiments 1 to 7, wherein each nozzle opening has a diameter between 0.1 mm and 3.2 mm.

[0142]

[0156] Embodiment 9. The liquid impinger of any one of embodiments 1-8, wherein at least one nozzle comprises a shape that includes a circular arc.

[0143]

[0157] Embodiment 10. The liquid impinger of embodiment 9, wherein the arc substantially lies in a plane that forms an angle of between 85° and 95° with the vertical axis.

[0144]

[0158] Aspect 11. A liquid impinger according to any one of aspects 1-10, wherein the gas inlet is connected to at least one nozzle by a tube extending therein from top to bottom.

[0145]

[0159] Embodiment 12. A liquid impinger as described in embodiment 11, wherein the tube is substantially straight along the vertical axis.

[0146]

[0160] Aspect 13. The liquid impinger of aspect 11 or 12, wherein the gas flow path is bent at an angle of 80° to 100° between the tube and the at least one nozzle.

[0147]

[0161] Embodiment 14. A liquid impinger according to any one of embodiments 1 to 13, wherein at least one nozzle has a horizontal angle between 0° and 40°.

[0148]

[0162] Embodiment 15. The liquid impinger of any one of embodiments 1 to 14, wherein at least one nozzle has a vertical angle between -40° and 40°.

[0149]

[0163] Embodiment 16. A liquid impinger according to any one of embodiments 1-15, wherein the lower portion comprises a cylindrical wall extending along at least a portion of a substantially vertical axis.

[0150]

[0164] Aspect 17. A liquid impinger as described in any one of aspects 1 to 16, further comprising at least one extension between the lower portion and the upper portion, the extension having a maximum widening point having an internal cross-sectional area greater than the internal cross-sectional area of ​​the maximum widening point of the lower portion.

[0151]

[0165] Aspect 18. A liquid impinger as described in aspect 17, wherein the extension is substantially spherical or elliptical in shape.

[0152]

[0166] Aspect 19. A liquid impinger as described in aspect 17 or 18, further comprising at least one tapered section between the extension section and the top, the at least one tapered section tapering along a vertical axis to a smaller internal cross-sectional area toward the top.

[0153]

[0167] Embodiment 20. The liquid impinger of any one of embodiments 17-19, further comprising at least one substantially straight wall component between the expansion portion and the tapered portion.

[0154]

[0168] Embodiment 21. The liquid impinger of any one of embodiments 1-15, wherein the lower portion comprises a substantially spherical or elliptical shape.

[0155]

[0169] Aspect 22. A liquid impinger as described in aspect 21, further comprising at least one tapered section between the lower portion and the upper portion, the at least one tapered section tapering along a vertical axis to a smaller internal cross-sectional area toward the upper portion.

[0156]

[0170] Aspect 23. A liquid impinger according to any one of aspects 1 to 22, wherein the lower portion further comprises a sidewall, and the nozzle opening is disposed within 10 mm of the sidewall or substantially flush with the sidewall.

[0157]

[0171] Aspect 24. A liquid impinger according to any one of aspects 1 to 23, wherein the liquid impinger is configured to operate with a volume of liquid between 15 mL and 200 mL.

[0158]

[0172] Aspect 25. A liquid impinger as described in any one of aspects 1 to 24, wherein at least a portion of the liquid impinger is constructed from a material that is sufficiently transparent to radiation to permit sterilization of the liquid (if present) and interior by irradiation.

[0159]

[0173] Aspect 26. A liquid impinger as described in any one of aspects 1 to 25, wherein a lower portion is configured to be attached to or detached from the liquid impinger by screw-drive rotation along the threads of the lower portion of the liquid impinger.

[0160]

[0174] Embodiment 27. A liquid impinger according to any one of embodiments 1 to 26, configured to be used once to monitor a gas flow and then discarded.

[0161]

[0175] Aspect 28. A liquid impinger according to any one of aspects 1 to 27, wherein the liquid comprises an antifoaming agent, and optionally the antifoaming agent is present in the liquid at a concentration of 0.001% to 1% by volume.

[0162]

[0176] Aspect 29. A liquid impinger according to any one of aspects 1 to 28, wherein the container comprises a sampling port configured to enable sampling of liquid in the container by selective access to the liquid within the container.

[0163]

[0177] Embodiment 30. A liquid impinger as described in embodiment 29, wherein the container includes a removable cap for sealing the sampling port.

[0164]

[0178] Aspect 31. A liquid impinger as described in aspect 30, wherein the cap includes a septum configured to receive a needle to permit withdrawal of liquid from the interior of the container while maintaining the interior of the container sealed.

[0165]

[0179] Aspect 32. The liquid impinger according to any one of aspects 1 to 31. a vessel including a vertical axis, an upper portion, an interior portion containing a liquid, and a lower portion including an interior base; a gas inlet disposed within the interior and in fluid communication with the interior through at least one nozzle attached to the lower portion, the nozzle including a nozzle opening, the nozzle opening being submerged in the liquid; and a gas outlet in fluid communication with the interior; providing a liquid impinger comprising a gas inlet, at least one nozzle, an interior, and a gas outlet, which in turn define a gas flow path; transporting a gas containing a test substance along a gas flow path within a liquid; precipitating at least a portion of the test substance in a liquid; The method includes:

[0166]

[0180] Embodiment 33. The method of embodiment 32, wherein the test agent is a particle, a molecular test agent, or a combination thereof.

[0167]

[0181] Aspect 34. The method of aspect 32 or 33, wherein the liquid impinger comprises at least two components, and the method further comprises the step of filling the container with liquid prior to the providing step, either before or after assembly of the at least two components.

[0168]

[0182] Aspect 35. A method according to any one of aspects 32 to 34, further comprising the step of irradiating the liquid impinger in assembled and / or filled form with radiation prior to the transporting step to sterilize at least a portion of its interior and at least a portion of the liquid contained therein, wherein at least a portion of the liquid impinger is constructed of a material that is sufficiently transparent to radiation to enable sterilization.

[0169]

[0183] Embodiment 36. The method of any one of embodiments 32 to 35, wherein at least a portion of the test substances comprises biological particles.

[0170]

[0184] Embodiment 37. The method of any one of embodiments 32 to 36, further comprising, after the precipitating step, culturing the liquid under conditions sufficient to promote growth of biological particles, wherein the liquid comprises a growth medium.

[0171]

[0185] Aspect 38. The method of aspect 37, further comprising detecting whether biological particles are present in the liquid.

[0172]

[0186] Aspect 39. The method of aspect 38, wherein the detecting step includes at least one of: (1) optical detection including at least one of visual inspection by eye, use of an optical detector, an imager, ultraviolet-visible, near-infrared, infrared, or fluorescence spectroscopy; (2) recognition of changes in oxygen or carbon dioxide levels in the liquid; or (3) analysis of the liquid following extraction from the liquid impinger, optionally using laboratory techniques including polymerase chain reaction (PCR), nucleotide sequencing, hybridization, restriction fragment length polymorphism (RFLP) analysis, flow cytometry, fluorescent in-situ hybridization (FISH), immunological identification, fatty acid profiling, metabolic profiling, or any combination thereof.

[0173]

[0187] Aspect 40. The method of any one of aspects 36-39, wherein at least one of the culturing step or the detecting step is performed without removal of liquid from the container or disassembly of the liquid impinger.

[0174]

[0188] Aspect 41. The method according to any one of aspects 34 to 37, wherein the combined execution of the filling step and the sterilizing step minimizes human contact with the liquid and reduces false positives in the detecting step.

[0175]

[0189] Aspect 42. The method of any one of aspects 34 to 38, further comprising, after performing one cycle of the steps of preparing, transporting, precipitating, incubating, and detecting, at least one of the following steps: (1) discarding the liquid impinger; (2) not again sterilizing the liquid impinger in preparation for a second cycle of the steps of preparing, transporting, precipitating, incubating, and detecting; or (3) not again performing the second cycle of the steps of preparing, transporting, precipitating, incubating, and detecting.

[0176]

[0190] Embodiment 43. The method of any one of embodiments 32 to 42, wherein the at least one nozzle comprises at least two nozzles or at least three nozzles.

[0177]

[0191] Embodiment 44. The method of any one of embodiments 32 to 43, wherein each nozzle opening has a diameter of 0.1 mm to 3.2 mm.

[0178]

[0192] Embodiment 45. The method of any one of embodiments 32 to 44, wherein at least one nozzle comprises a shape that includes a circular arc, the arc substantially lying in a plane that forms an angle of 85° to 95° with a vertical axis.

[0179]

[0193] Embodiment 46. The method of any one of embodiments 32 to 45, wherein at least one nozzle has a horizontal angle of between 0° and 40°.

[0180]

[0194] Embodiment 47. The method of any one of embodiments 32 to 46, wherein the gas inlet is connected to at least one nozzle by a tube extending therein from top to bottom.

[0181]

[0195] Embodiment 48. The lower portion comprises a cylindrical, spherical, or elliptical shape, and the liquid impinger is: At least one extension between the lower portion and the upper portion, the extension having a maximum widening point that has a larger internal cross-sectional area than the internal cross-sectional area of ​​the maximum widening point of the lower portion; at least one tapered section between the extension section and the top section, the at least one tapered section tapering along a vertical axis to a smaller internal cross-sectional area toward the top section; The method according to any one of embodiments 32 to 47, further comprising:

[0182]

[0196] Embodiment 49. The method of any one of embodiments 32 to 48, wherein the lower portion further comprises a sidewall, and the nozzle opening is disposed within 10 mm of the sidewall or substantially flush with the sidewall.

[0183]

[0197] Aspect 50. A method according to any one of aspects 32 to 49, wherein the conveying step is carried out at a flow rate of 1 L / min to 20 L / min.

[0184]

[0198] Embodiment 51. The method of any one of embodiments 32 to 50, wherein the liquid impinger comprises a polymeric material.

[0185]

[0199] Aspect 52. The method of aspect 51, wherein the polymeric material comprises poly(acrylonitrile-butadiene-styrene), polyethylene, polycarbonate, polyamide, polystyrene, transparent polystyrene (e.g., Polystyrol™), high impact polystyrene, polypropylene, polyoxymethylene, polyurethane, rubber, or any combination thereof.

[0186]

[0200] Aspect 53. A method according to any one of aspects 32 to 52, comprising the step of removing a sample of liquid from the interior of the container via a sampling port in response to the moving step.

[0187]

[0201] Aspect 54. The method of aspect 53, wherein the step of removing the sample includes inserting a needle into a septum of the sample port.

[0188]

[0202] 55. A method for generating a liquid impinger, comprising: forming at least two components of a liquid impinger; Optionally, creating an assembled liquid impinger by assembling at least two components, the assembled liquid impinger comprising: a vessel including a vertical axis, an upper portion, an interior portion, and a lower portion including an interior base; a gas inlet disposed within the interior and in fluid communication with the interior through at least one nozzle attached to the lower portion, the nozzle including a nozzle opening; and a gas outlet in fluid communication with the interior; Equipped with the gas inlet, the at least one nozzle, the interior, and the gas outlet, in turn, define a gas flow path; a container configured to contain a liquid therein; Optionally, filling a portion of the interior of the assembled liquid impinger with liquid to create a filled liquid impinger; Optionally, exposing the filled liquid impinger to radiation to sterilize at least a portion of the liquid present within the liquid impinger, thereby producing a filled and sterile liquid impinger; Optionally, either before or after the exposing step, packaging the filled liquid impinger or the filled and sterile liquid impinger in a manner that prevents ingress of particles or contamination into the interior of the liquid impinger; A method comprising:

[0189]

[0203] 56. A method for producing a filling and sterilizing liquid impinger, comprising: A first providing step includes providing a filled liquid impinger, the filled liquid impinger comprising: a vessel including a vertical axis, an upper portion, an interior portion, and a lower portion including an interior base; a gas inlet disposed within the interior and in fluid communication with the interior through at least one nozzle attached to the lower portion, the nozzle including a nozzle opening; and a gas outlet in fluid communication with the interior; Equipped with the gas inlet, the at least one nozzle, the interior, and the gas outlet, in turn, define a gas flow path; a container containing a liquid therein; exposing the filled liquid impinger to radiation to sterilize at least a portion of the liquid present within the liquid impinger, thereby producing a filled and sterile liquid impinger; Optionally, either before or after the exposing step, packaging the filled liquid impinger or the filled and sterile liquid impinger in a manner that prevents ingress of particles or contamination into the interior of the liquid impinger; A method comprising:

[0190]

[0204] Aspect 57. Prior to the first providing step, a second providing step including providing an assembled liquid impinger, the assembled liquid impinger including a filled liquid impinger without liquid; filling a portion of an interior of the assembled liquid impinger with liquid to create a filled liquid impinger; 57. The method of embodiment 56, further comprising:

[0191]

[0205] Aspect 58. The method of aspect 57, further comprising, prior to the second providing step, creating an assembled liquid impinger by assembling at least two components.

[0192]

[0206] Embodiment 59. The method of embodiment 58, further comprising the step of forming at least two components prior to the assembling step.

[0193]

[0207] 60. A method for producing a filling and sterilizing liquid impinger, comprising: forming at least two components of a liquid impinger; creating an assembled liquid impinger by assembling at least two components, the assembled liquid impinger comprising: a vessel including a vertical axis, an upper portion, an interior portion, and a lower portion including an interior base; a gas inlet disposed within the interior and in fluid communication with the interior through at least one nozzle attached to the lower portion, the nozzle including a nozzle opening; and a gas outlet in fluid communication with the interior; Equipped with the gas inlet, the at least one nozzle, the interior, and the gas outlet, in turn, define a gas flow path; a container configured to contain a liquid therein; filling a portion of an interior of the assembled liquid impinger with liquid to create a filled liquid impinger; exposing the filled liquid impinger to radiation to sterilize at least a portion of the liquid present within the liquid impinger, thereby producing a filled and sterile liquid impinger; Optionally, either before or after the exposing step, packaging the filled liquid impinger or the filled and sterile liquid impinger in a manner that prevents ingress of particles or contamination into the interior of the liquid impinger; A method comprising:

[0194]

[0208] Aspect 61. The method of aspect 60, wherein a packaging step is performed and includes (1) attaching a cap to one or more gas inlets and gas outlets, (2) sealing a filled liquid impinger or a filled and sterilized liquid impinger in a container, or (3) a combination thereof.

[0195]

[0209] Aspect 62. The method of aspect 60 or 61, wherein the forming step is performed and includes molding, injection molding, blow molding, rotational molding, additive manufacturing, 3D printing, subtractive manufacturing, casting, molding, vacuum forming, extrusion, or any combination thereof.

[0196]

[0210] Embodiment 63. The method of any one of embodiments 60-62, wherein a forming step is performed to form one or more polymeric materials into at least two components.

[0197]

[0211] Aspect 64. The method of aspect 63, wherein the one or more polymeric materials comprise poly(acrylonitrile-butadiene-styrene), polyethylene, polycarbonate, polyamide, polystyrene, transparent polystyrene (e.g., Polystyrol™), high impact polystyrene, polypropylene, polyoxymethylene, polyurethane, rubber, or any combination thereof.

[0198]

[0212] Embodiment 65. The method of any one of embodiments 60 to 64, wherein the at least two components include three components.

[0199]

[0213] Aspect 66. The method of any one of aspects 60 to 65, wherein the radiation comprises beta rays, gamma rays, X-rays, electron beam rays, or any combination thereof.

[0200]

[0214] Embodiment 67. The method of any one of embodiments 60 to 66, wherein the liquid comprises a growth medium.

[0201]

[0215] Aspect 68. The method of any one of aspects 60-67, further comprising the step of sterilizing the at least two components, the assembled liquid impinger, or both, with radiation prior to the filling step, the radiation comprising beta radiation, gamma radiation, x-rays, electron beam radiation, or any combination thereof.

[0202]

[0216] All references throughout this application (e.g., patent documents, including issued or patented patents or equivalents, published patent applications, and source documents such as non-patent documents) are each incorporated herein in their entirety as if individually incorporated by reference, to the extent that each reference is at least partially consistent with the disclosure of this application (e.g., a reference that is partially inconsistent is incorporated by reference except for that partially inconsistent portion).

[0203]

[0217] The terms and expressions employed herein are used as terms of description and are not limiting in any way, and the use of such terms and expressions is not intended to exclude any equivalents of the features shown and described or portions thereof, but it is recognized that various improvements are possible within the scope of the claims of the present invention. Thus, although the present invention has been specifically disclosed by preferred embodiments, exemplary embodiments, and optional features, it is understood that improvements and modifications of the concepts disclosed herein may be made by those skilled in the art, and that such improvements and modifications are considered to be within the scope of the present invention as defined in the appended claims. The specific embodiments described herein are examples of useful embodiments of the present invention, and it will be apparent to those skilled in the art that the present invention can be practiced using many variations of the devices, device components, and method steps described herein. As will be apparent to those skilled in the art, the method and the devices useful for the method may include many optional configurations, processing elements, and steps.

[0204]

[0218] As used herein, in the appended claims, the singular forms "a," "an," and "the" include plural references 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. Additionally, the terms "a" (or "an"), "one or more," and "at least one" may be used interchangeably herein. Additionally, the terms "comprising," "including," and "having" may be used interchangeably. The phrase "of any of claims XX-YY" (XX and YY represent claim numbers) is intended to provide an alternative form of multiple dependent claim, and in some embodiments may be used interchangeably with the phrase "as in any one of claims XX-YY."

[0205]

[0219] When a Markush group or other group is used herein, it is intended that all individual members of the group and all possible combinations and subcombinations of the group are individually included in the disclosure. Also, unless otherwise specified, all isotopic variations of the compounds disclosed herein are intended to be encompassed by this disclosure. For example, it is understood that any hydrogen or hydrogens in the disclosed molecules can be replaced with deuterium or tritium. Isotopic variations of molecules are generally useful as standards in the analysis of the molecule and in chemical and biological studies related to the molecule or its use. Methods for making such isotopic variations are known in the art. The specific names of the compounds are exemplary, since those skilled in the art know that the same compound can be given different names.

[0206]

[0220] Any device, system, process, combination of components, or method described or illustrated herein can be used to practice the present invention, unless otherwise stated.

[0207]

[0221] Whenever a range is given herein (e.g., a temperature range, a time range, a composition range, or a concentration range), all intermediate ranges and subranges, as well as all individual values ​​within the given range, are intended to be included in the disclosure. It is understood that any subranges contained in the description herein, and any individual values ​​within a range or subrange, may be excluded from the claims.

[0208]

[0222] All patents and publications cited herein demonstrate the skill of those skilled in the art to which this invention pertains. References cited herein are incorporated herein in their entirety to indicate the prior art as of their respective publication or filing dates, and this information may be incorporated herein, if necessary, to exclude specific embodiments in the prior art. For example, when claiming a composition, it is understood that compounds known and available in the art prior to Applicant's invention, including compounds for which enabling disclosures are provided in the references cited herein, are not included in the claimed composition.

[0209]

[0223] As used herein, "comprising" is synonymous with "including," "containing," or "characterized by," and is inclusive or open-ended, and does not exclude additional unrecited elements or method steps. As used herein, "consisting of" excludes any element, step, or ingredient not specified in the claim element. As used herein, "consisting essentially of" does not exclude materials or steps that do not materially affect the basic and novel characteristics of the claim. In any instance herein, the terms "comprising," "consisting essentially of," and "consisting of" may each be substituted with either of the other two terms. The invention illustratively described herein may be suitably practiced in the absence of any element or elements, limitations, if any, not specifically disclosed herein.

[0210]

[0224] It will be appreciated by those skilled in the art that starting materials, biological materials, reagents, synthesis methods, purification methods, analytical methods, testing methods, and biological methods not specifically exemplified can be employed in the practice of the present invention without undue experimentation. All functional equivalents known in the art of any such materials and methods are intended to be encompassed by the present invention. The terms and expressions employed are used as terms of description and are not limiting in any way, and the use of such terms and expressions is not intended to exclude any equivalents of the features shown and described or portions thereof, but is recognized as being capable of various modifications within the scope of the claims of the present invention. Thus, although the present invention has been specifically disclosed by preferred embodiments and optional features, it is to be understood that improvements and modifications of the concepts disclosed herein may be made by those skilled in the art, and that such improvements and modifications are considered to be within the scope of the present invention as defined in the appended claims.

Claims

1. A container having a lower part including a vertical axis, an upper part, an interior, and an interior base, and a gas inlet disposed within the interior and in fluid communication with the interior via at least one nozzle attached to the lower part, the nozzle including a nozzle opening, the gas inlet, and a gas outlet in fluid communication with the interior, and a liquid contained within the interior, comprising a liquid injector, wherein the gas inlet, the at least one nozzle, the interior, and the gas outlet sequentially define a gas flow path, and the nozzle is configured such that the gas passes through the liquid by conveyance of the gas along the gas flow path. A liquid injector.

2. comprising a polymeric material, wherein the polymeric material includes poly(acrylonitrile-butadiene-styrene), polyethylene, polycarbonate, polyamide, polystyrene, transparent polystyrene (e.g., Polystyrol (trademark)), high-impact polystyrene, polypropylene, polyoxymethylene, polyurethane, rubber, or any combination thereof. The liquid injector according to claim 1.

3. The liquid injector according to claim 1, comprising a material transparent to beta rays.

4. The liquid injector according to claim 1, wherein the liquid is sterilized by radiation.

5. The liquid injector according to claim 1, wherein the at least one nozzle includes a shape including an arc, and the arc is substantially within a plane forming an angle of 85° to 95° with the vertical axis.

6. The liquid injector according to claim 1, wherein the gas inlet is connected to the at least one nozzle by a tube extending from the upper part to the lower part within the interior, and the gas flow path bends at an angle of 80° to 100° between the tube and the at least one nozzle.

7. The liquid injector according to claim 1, further comprising at least one expansion part between the lower part and the upper part, wherein a maximum width point of the expansion part has an internal cross-sectional area larger than an internal cross-sectional area of a maximum width point of the lower part.

8. At least one tapered portion between the extension portion and the upper portion, the at least one tapered portion tapering so as to have a smaller internal cross-sectional area toward the upper portion along the vertical axis, the liquid injector according to claim 7, further comprising at least one tapered portion.

9. The liquid injector according to claim 1, wherein the lower portion further comprises a side wall, and the nozzle opening is disposed within 10 mm of the side wall or substantially in the same plane as the side wall.

10. The liquid injector according to claim 1, wherein at least a part of the liquid injector is made of a material that is sufficiently transparent to radiation in order to enable sterilization of the liquid (if present) and the interior by irradiation.

11. The liquid injector according to claim 1, wherein the container comprises a sampling port configured to enable sampling of the liquid in the container by selective access to the liquid in the interior of the container.

12. The liquid injector according to claim 11, wherein the container comprises a removable cap for sealing the sampling port.

13. The liquid injector according to claim 12, wherein the cap comprises a diaphragm configured to receive a needle and enable withdrawal of liquid from the interior of the container while maintaining the interior of the container in a sealed state.

14. A step of flowing a gas containing a test substance through a liquid injector, the liquid injector comprising a container having a vertical axis, an upper portion, an interior containing a liquid, and a lower portion including an interior base; a gas inlet disposed in the interior and in fluid communication with the interior through at least one nozzle attached to the lower portion, the nozzle including a nozzle opening, the nozzle opening being immersed in the liquid; a gas outlet in fluid communication with the interior; wherein the gas inlet, the at least one nozzle, the interior, and the gas outlet sequentially define a gas flow path; a step of contacting the gas with the liquid; a step of moving at least a part of the test substance from the gas to the liquid in response to the contact; A method comprising.

15. The method according to claim 14, wherein the test substance is a particle, a molecular test substance, or a combination thereof, and at least a part of the test substance contains biological particles.

16. The method according to claim 14, wherein the liquid injector comprises at least two components, and the method further comprises a step of filling the container with the liquid either before or after the assembly of the at least two components prior to the step of preparing.

17. Prior to the step of transporting, a step of sterilizing at least a part of the interior and at least a part of the liquid contained therein by irradiating the liquid injector in an assembled form and / or a filled form with radiation, wherein at least a part of the liquid injector is made of a material sufficiently transparent to the radiation to enable the sterilization, the method according to claim 14 further comprising the step.

18. After the step of moving, a step of culturing the liquid under conditions sufficient to promote the growth of biological particles, wherein the liquid comprises a growth medium, the method according to claim 14 further comprising the step.

19. The method according to claim 15, further comprising a step of detecting whether the biological particles are present in the liquid.

20. The step of detecting includes at least one of (1) visual inspection by eye, optical detection using an optical detector, an imaging device, ultraviolet-visible, near-infrared, infrared, or fluorescence spectroscopy, (2) recognition of a change in the oxygen level or carbon dioxide level in the liquid, or (3) optionally polymerase chain reaction (PCR), nucleotide sequencing, hybridization, restriction fragment length polymorphism (RFLP) analysis, flow cytometry, fluorescence in-situ hybridization (FISH), immunological identification, fatty acid profiling, metabolic profiling, or analysis of the liquid after extraction from the liquid injector using analytical laboratory techniques including any combination thereof, the method according to claim 19.

21. The method according to claim 18, wherein at least one of the step of culturing or the step of detecting is performed without removing the liquid from the container or disassembling the liquid injector.

22. The method according to claim 14, wherein the gas inlet is connected to the at least one nozzle by a tube extending from the upper part to the lower part inside the same.

23. The method according to claim 14, comprising the step of taking out a sample of the liquid from inside the container through a sampling port in response to the step of moving.

24. The method according to claim 23, wherein the step of taking out the sample includes inserting a needle into a septum of the sampling port.

25. A method for producing a filled and sterilized liquid syringe, comprising: forming at least two components of a liquid syringe; generating an assembled liquid syringe by assembling the at least two components, the assembled liquid syringe including: a container including a lower part having a vertical axis, an upper part, an interior, and a base inside; a gas inlet disposed inside and in fluid communication with the interior through at least one nozzle attached to the lower part, the nozzle including a nozzle opening, the gas inlet; a gas outlet in fluid communication with the interior; and the gas inlet, the at least one nozzle, the interior, and the gas outlet sequentially define a gas flow path; the step of configuring the container to contain a liquid inside; generating a filled liquid syringe by filling a part of the interior of the assembled liquid syringe with the liquid; generating the filled and sterilized liquid syringe by exposing the filled liquid syringe to radiation to sterilize at least a part of the liquid present inside the liquid syringe; optionally, packaging the filled liquid syringe or the filled and sterilized liquid syringe to prevent intrusion of particles or contamination into the interior of the liquid syringe either before or after the exposing step; and including.

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