Robotic Control for Particle Sampling and Monitoring

Abstract

Systems and methods for controlled environment sampling, including automated and / or robotically controlled sampling, are provided herein. The systems and methods are useful for determining the presence, quantity, size, concentration, viability, species, or characteristics of particles, including viable biological particles, within a controlled environment. The described systems and methods may utilize rotational motion via robotics, automation, and / or control systems to reduce or eliminate some or all steps performed by a human operator in traditional particle collection and / or analysis methodologies. The described systems and methods may utilize rotational motion via robotics, automation, and / or control systems to provide particle sampling over a well-defined time period for an individual impactor and / or sequential sampling with multiple impactors.

Description

[Background technology]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to U.S. Provisional Patent Application No. 63 / 476,338, filed December 20, 2022, and U.S. Provisional Patent Application No. 63 / 479,522, filed January 11, 2023, each of which is incorporated by reference in its entirety into this specification.

[0002] Incorporation by Reference

[0002] References, each of which is incorporated herein in its entirety to the extent not inconsistent with this specification, including U.S. Patent No. 10,345,200 issued on July 9, 2019, U.S. Patent No. 11,231,345 issued on January 25, 2022, U.S. Patent No. 11,255,760 issued on February 22, 2022, and U.S. Patent Application Publication No. 20210223273 published on July 22, 2021, relate to particle sampling, analysis, automation, and robotic control.

[0003] The present invention is in the field of particle sampling, collection and analysis. The present invention relates generally to systems and methods for robotic control, automation and handling for particle samplers and counters for characterizing particles in air and other gases in controlled environments, including clean room and sterile manufacturing environments.

[0004]

[0004] Clean rooms and clean zones are commonly used in a wide range of industries, including microelectronics, semiconductors, pharmaceutical, biological, and medical device manufacturing, cosmetics, and food and beverage. In the semiconductor industry, for example, particles deposited on semiconductor wafers can affect or interfere with small-scale manufacturing processes, resulting in decreased production efficiency. Meanwhile, in the pharmaceutical industry, which lacks this type of real-time efficiency feedback, contamination with airborne particles and biological contaminants puts pharmaceutical products at risk of failing to meet cleanliness level standards established by the U.S. Food and Drug Administration (FDA) and other foreign and international health regulatory authorities.

[0005]

[0005] Standards for classifying cleanroom particle levels, as well as 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 clean zones, while liquid particle counters are used to optically measure particle contamination levels in process fluids. Where microbiological particles are of particular concern, such as in the pharmaceutical industry, not only is quantifying the number of airborne particles important, but characterizing the viability and identity of microbiological particles is also an issue. ISO 14698-1 and 14698-2 provide standards for the evaluation of cleanroom and clean zone environments for biological contaminants.

[0006] In at least some sterile, aseptic, or clean room environments, humans are routinely present within the environment to perform certain operations. For example, when manufacturing a barrier system, humans may be required to operate machinery, manipulate objects, and otherwise interact with items placed within the barrier system. The presence of humans within such environments inevitably increases the risk of particulate and biological contamination levels. To limit or eliminate human interaction, controlled environment systems are increasingly transitioning to automated or robotic systems. Many applications requiring controlled environments also require or utilize human-operated environmental sampling to ensure that viable and non-viable particles and / or microorganisms remain below desired levels. As the need for lower viable and non-viable particle concentrations increases due to increasing quality standards and government regulatory requirements, more sophisticated sampling techniques are needed to reduce false positives and the risk of external contamination from human interaction within the controlled environment.

[0007]

[0007] From the above, it can be seen that there remains a need in the art for particle collection, analysis, and characterization systems for sampling and collecting particles and / or microorganisms from controlled environments with reduced human interaction to reduce the risk of further contamination. These systems may include particle collection and analysis within robotic limited-access barrier systems or other automated controlled environment process components. Summary of the Invention

[0008]

[0008] Provided herein are systems and methods for sampling of controlled environments, including automated and / or robotically controlled sampling. The systems and methods are useful for determining the presence, quantity, size, concentration, viability, species, or characteristics of particles, including viable biological particles, within a controlled environment. The described systems and methods may utilize rotational motion by robotics, automation, and / or control systems to reduce or eliminate some or all steps performed by a human operator in traditional particle collection and / or analysis methodologies. The described systems and methods may include rotational motion by robotics, automation, and / or control systems to provide sampling of particles over a well-defined period for an individual impactor and / or sequential sampling by multiple impactors.

[0009] The provided systems and methods are compatible with various controlled environments, including sterile environments, e.g., restricted access barrier systems (RABS) and isolator systems. These systems and methods allow integration with impactors within controlled environments for locating, connecting, transporting, operating, sampling, and / or analyzing environmental conditions within the controlled environment with limited or no human contact. Thus, the described systems and methods reduce the risk of contamination from particles or organisms present on the operator. The described systems and methods may provide for sampling and identification of viable biological particles with reduced false positives.

[0010] In one aspect, a robotic sampling system for sampling particles, such as biological particles, within an enclosure is provided, the system comprising: (i) (a) a sampling head having one or more intake openings for sampling a stream of air and / or other gas within the enclosure; (b) an impactor base including a growth medium for receiving particles, such as biological particles, from the stream of air and / or other gas, the growth medium having an impact surface for receiving particles from the stream of air and / or other gas; and (c) one or more intake openings. (d) an impactor for holding the growth medium, the impactor having a selectively removable cover for covering the mouth, and an outlet for discharging a stream of air and / or other gas; and (ii) a robotic manipulator system configured to rotate the impactor from a rest position to a sampling position, optionally the robotic manipulator system including one or more processors and / or device components, such as implemented by software and / or hardware, for controlling the integration, rotation, actuation, cover removal, transport, fluid flow formation, cover closing, and / or impactor removal.

[0011] In one embodiment, the system is provided in fluid communication with the enclosure. In one embodiment, the system is provided within the enclosure.

[0012] In some embodiments, the system includes multiple impactors, and the system can control multiple samplers to provide sequential sampling, continuous sampling, and / or sampling of each impactor over a well-defined time frame. In some embodiments, the system includes 1 to 1000 impactors. In some embodiments, the impactor that has undergone sampling is removed from the system, e.g., for analysis of biological particles. In some embodiments, a new impactor is provided to the system, e.g., to provide sequential and / or continuous sampling. In some embodiments, the impactors are single-use and / or disposable devices.

[0013] In some embodiments, the selectively removable cover of the sampler includes a magnet configured to magnetically engage with a robotic manipulator system. In some embodiments, the robotic manipulator system is configured to remove the selectively removable cover with the magnet and / or to replace the selectively removable cover with the magnet. In some embodiments, the system further includes a robotic arm, the robotic arm including a magnetic engagement mechanism for engaging with the magnet of the selectively removable cover. In some embodiments, the magnetic engagement mechanism includes one or more electromagnets, such as 1 to 10 electromagnets, optionally 1 to 5 electromagnets.

[0014] In some embodiments, the selectively removable cover of the sampler includes a lever configured to facilitate removal of the selectively removable cover by a robotic arm, hi some embodiments, the lever includes a groove configured to engage a gripping element of the robotic arm.

[0015] In some embodiments, the system is configured to sequentially rotate the samplers into sampling positions and / or provide continuous sampling conditions. In some embodiments, the system is configured to robotically remove a used impactor (e.g., a sampler that has sampled fluid from the enclosure for a selected and / or well-defined period of time) from the robotic manipulator system and robotically replace the used impactor with one or more new impactors in a manner that provides sampling for each sampler sequentially or over a well-defined period of time. In some embodiments, the robotic manipulator system is configured to (i) rotate a first impactor of the multiple impactors from a sampling position to a rest position and (ii) rotate a second impactor of the multiple impactors from the rest position to a sampling position, optionally wherein the system is configured to perform steps (i) and (ii) simultaneously.

[0016] In some embodiments, the robotic manipulator system is configured to rotate the impactors sequentially, simultaneously, and / or continuously. In some embodiments, the sampling position of the first impactor has the same location and orientation as the sampling position of the second impactor. The impactor is locked by three reference points, with the rotor at the center. The first point is a suction hole, where a "hose nozzle" is inserted into a special suction hole in the rotor. The second point consists of a support shaped to allow the impactor to rest on its bottom with at least two points preventing rotation. The third point consists of a lock made of two pins that prevents its vertical movement after it is inserted into the housing.

[0017] In some embodiments, the system rotates the impactor along a well-defined and / or repeatable trajectory, for example, so that at least a portion of the impactor is located in substantially the same location and / or orientation during sampling. In some embodiments, the system is configured to rotate the impactor along a trajectory that traces a portion of a complete circle or a complete circle. In some embodiments, the robotic manipulator system rotates the impactor from a rest position to a sampling position, the impactor having a trajectory characterized by an arc having an arc length selected from 10 to 180 degrees. In some embodiments, the robotic manipulator system rotates the impactor from a rest position to a sampling position, the impactor having a trajectory characterized by an arc with an arc length equal to 360 degrees divided by the maximum number of impactors the system is configured to hold. In one embodiment, the robotic manipulator system is configured to hold three impactors, and the robotic manipulator system rotates the impactor from a rest position to a sampling position, the impactor having a trajectory characterized by an arc with an arc length of 120 degrees.

[0018] In some embodiments, the rotation is about a horizontal axis. In some embodiments, the rotation is about a vertical axis. In some embodiments, the impact surface is oriented horizontally when the impactor is in the sampling position. In some embodiments, the impact surface is oriented vertically when the impactor is in the rest position. In some embodiments, the system further comprises a flow system for flowing fluid through the particle detection device. The flow system may comprise a pump, a vacuum, a blower, a fluid actuator, and / or a house vacuum line.

[0019] In some embodiments, the flow system is configured to initiate flow through the impactor in response to the robotic manipulator system manipulating the impactor to a sampling position and / or removing a selectively removable cover. In some embodiments, the flow system is configured to stop flow through the impactor in response to expiration of a predetermined sampling duration. In some embodiments, the robotic manipulator system is configured to replace the selectively removable cover in response to cessation of flow through the impactor and / or expiration of the predetermined duration. In some embodiments, the predetermined duration is selected from the range of 1 to 1,000 hours. In some embodiments, the robotic manipulator system is configured to maneuver the used impactor to a rest position in response to replacing the selectively removable cover. In some embodiments, in response to maneuvering the used impactor to a rest position, the robotic manipulator system is configured to maneuver a new impactor to a sampling position and / or remove a selectively removable cover from the new impactor. The flow system can then begin flow through the new impactor. Thus, in some embodiments, the system can provide essentially continuous autonomous sampling through the sequential use of multiple impactors. In some embodiments, the essentially continuous autonomous sampling through the sequential use of multiple impactors has a predetermined duration of 1 to 10,000 hours.

[0020] In some embodiments, the system further comprises a rotor mechanism configured to engage a plurality of impactors disposed thereon, the impactors being oriented about a rotational axis of the rotor mechanism, and the rotor mechanism configured to rotate about the rotational axis. In one embodiment, the rotational axis is substantially horizontal. For example, in one embodiment, the rotational axis is within 10 degrees of horizontal. In one embodiment, the rotational axis is within 5 degrees of horizontal.

[0021] In one embodiment, each impactor has a bottom surface facing the impact surface, and each impactor is positioned on the rotor mechanism such that the bottom surface of each impactor faces toward the axis of rotation. In one embodiment, the system is configured such that when the impactors are rotated to the sampling orientation, the impact surfaces of the impactors are substantially horizontal and point upward, and the impactors are located at the highest point on the rotational path followed by the rotor mechanism. In one embodiment, when the impactors are rotated to the rest position, the impact surfaces of the impactors are not substantially horizontal and / or do not face upward.

[0022] In one embodiment, the axis of rotation is substantially vertical. For example, in one embodiment, the axis of rotation is within 10 degrees of vertical. In one embodiment, the axis of rotation is within 5 degrees of vertical.

[0023] In one embodiment, the impact surface of each impactor remains substantially horizontal when rotated by the rotor mechanism from the rest position to the sampling position. In one embodiment, the multiple impactors are arranged on the rotor mechanism such that each impactor follows the same rotational path, the rotational paths defining a substantially horizontal plane.

[0024] In one embodiment, each impactor is positioned equidistant from the axis of rotation.

[0025] In some embodiments, the system further comprises a status indicator for indicating whether the system is in a sampling mode, a standby mode, and / or a sampling complete mode.

[0026] In some embodiments, the robotic manipulator system is configured to expose the inlet of the particle detection device to a fluid sample, such as one or more gases, from the enclosure, such as air, a process gas, a sterilant, and any combination thereof. In some embodiments, the robotic manipulator system is configured to collect particles from the particle detection device. In some embodiments, the robotic manipulator system is configured to operate the particle detection device in the absence of physical contact of the particle detection device by a user.

[0027] In some embodiments, the robotic manipulator system is configured to connect the particle detection device to a flow system. In some embodiments, the robotic manipulator system is configured to open the inlet to allow fluid flow to and through the particle detection device. In some embodiments, the particle detection device includes a cover for enclosing the inlet, and the robotic manipulator system is configured to remove the cover to allow fluid to enter the inlet. In some embodiments, the robotic manipulator system is configured to replace the cover to stop fluid from entering the inlet. In some embodiments, the robotic manipulator system is configured to close the inlet to stop fluid flow to the particle detection device.

[0028] In some embodiments, the flow system is located within a clean room or sterile environment, and the robotic manipulator system is configured to sample particles from a fluid, such as a gas, from an enclosure when no user is physically present within the clean room or sterile environment. In some embodiments, the robotic manipulator system is located within the clean room or sterile environment.

[0029] In some embodiments, the enclosure is a sterile enclosure, a restricted access barrier system (RABS), or a positive pressure isolator system. In some embodiments, the system is for detection of biological particles, such as microorganisms, in a fluid sample, such as a gas, in or from the enclosure, such as air, sterile air, process gas, sterilant, or any combination thereof.

[0030] The present system and method are compatible with a variety of impactor and sampling conditions, including non-laminar and substantially laminar sample flow conditions.

[0031]

[0031] In one aspect, a method for sampling particles, such as biological particles, in or from an enclosure is provided, the method comprising the steps of: (i) rotating an impactor from a rest position to a sampling position by a robotic manipulator system; (ii) removing a selectively removable cover over one or more intake openings of the impactor; and (iii) sampling a stream of air and / or other gas from or from the enclosure by the impactor, wherein the sampling step comprises: (a) taking in a stream of air and / or other gas by a sampling head having one or more intake openings; (b) impacting particles, such as biological particles, from the stream of air and / or other gas against an impaction surface of a growth medium in an impactor base of the impactor; and (c) exhausting the stream of air and / or other gas from the impactor through an outlet of the impactor, optionally wherein the rotating, removing, and sampling steps are performed and / or controlled by one or more processors and / or device components, e.g., implemented by software and / or hardware, for controlling the integration, rotation, actuation, cover removal, transport, fluid flow formation, cover closing, and / or removal of the impactor.

[0032] In one aspect, a method of controlling a robotic sampling system for sampling particles in an enclosure is provided, the method including the steps of: (i) providing a first instruction to the robotic manipulator system, the first instruction configured to cause the robotic manipulator system to rotate an impactor from a rest position to a sampling position; and (ii) providing a second instruction to the robotic manipulator system, the second instruction configured to cause the robotic manipulator system to remove a selectively removable cover from the impactor. and (iii) providing third instructions to the fluid actuation system, the third instructions configured to cause the fluid actuation system to draw air and / or other gas from the enclosure into the impactor, optionally the first instructions, second instructions, and / or third instructions originate from one or more processors and / or device components, e.g., implemented by software and / or hardware, for controlling integration, rotation, actuation, cover removal, transport, fluid flow formation, cover closing, and / or impactor removal.

[0033] While not wishing to be bound by any particular theory, beliefs or understandings of underlying principles related to the devices and methods disclosed herein may be discussed herein. It is recognized that regardless of the ultimate correctness of any mechanistic explanation or hypothesis, embodiments of the present invention may nevertheless be operable and useful. [Brief explanation of the drawings]

[0034] [Figure 1A] FIG. 1 is a top view of a first embodiment of a robotic sampling system. [Figure 1B] FIG. 1 is a side view of a first embodiment of a robotic sampling system. [Figure 2A]1A-1C are schematic diagrams illustrating the operation of a first embodiment of a robotic sampling system. [Figure 2B] 1A-1C are schematic diagrams illustrating the operation of a first embodiment of a robotic sampling system. [Figure 2C] 1A-1C are schematic diagrams illustrating the operation of a first embodiment of a robotic sampling system. [Figure 2D] 1A-1C are schematic diagrams illustrating the operation of a first embodiment of a robotic sampling system. [Figure 2E1] 1A-1C are schematic diagrams illustrating the operation of a first embodiment of a robotic sampling system. [Figure 2E2] 1A-1C are schematic diagrams illustrating the operation of a first embodiment of a robotic sampling system. [Figure 2F] 1A-1C are schematic diagrams illustrating the operation of a first embodiment of a robotic sampling system. [Figure 2G] 1A-1C are schematic diagrams illustrating the operation of a first embodiment of a robotic sampling system. [Figure 2H] 1A-1C are schematic diagrams illustrating the operation of a first embodiment of a robotic sampling system. [Figure 2I] 1A-1C are schematic diagrams illustrating the operation of a first embodiment of a robotic sampling system. [Figure 3A] FIG. 1 is a schematic diagram of one embodiment of an impactor useful in the present systems and methods. [Figure 3B] FIG. 1 is a schematic diagram of one embodiment of an impactor useful in the present systems and methods. [Figure 3C] FIG. 1 is a perspective view of a selectively removable cover of the impactor of the present invention. [Figure 3D] FIG. 3D is a bottom view of the selectively removable cover of FIG. 3C. [Figure 3E] 3C-3D are cross-sectional views of the selectively removable cover. [Figure 4] FIG. 10 is a side view of a second embodiment of a robotic sampling system. [Figure 5] FIG. 10 is a front view of a second embodiment of a robotic sampling system. [Figure 6] FIG. 10 is a rear view of a second embodiment of a robotic sampling system. [Figure 7] 10A-10D are side views of the process of loading an impactor into a second embodiment of a robotic sampling system. [Figure 8] FIG. 1 is an isometric view of a second embodiment of a robotic sampling system. [Figure 9] FIG. 10 is a front view of a third embodiment of a robotic sampling system. [Figure 10] FIG. 10 is a side view of a third embodiment of a robotic sampling system. [Figure 11] FIG. 10 is an isometric view of a third embodiment of a robotic sampling system. [Figure 12] 10A-10C illustrate one embodiment of a process for robotically removing a selectively removable cover of an impactor and positioning the impactor for sample collection. [Figure 13] 10A-10C illustrate one embodiment of a process for robotically removing a selectively removable cover of an impactor and positioning the impactor for sample collection. [Figure 14] 10A-10C illustrate one embodiment of a process for robotically removing a selectively removable cover of an impactor and positioning the impactor for sample collection. [Figure 15] 10A-10C illustrate one embodiment of a process for robotically removing a selectively removable cover of an impactor and positioning the impactor for sample collection. [Figure 16] FIG. 10 is a perspective view of a fourth embodiment of a robotic sampling system. [Figure 17] 1 illustrates an example of a robotic arm for removing and replacing a selectively removable cover.In the illustrated embodiment, the robotic arm includes a gripping element comprising a fork-like structure. [Figure 18]1 shows two different embodiments of sampling paths for viable and non-viable particles. In the embodiment on the left, the impactor is configured to rotate in a vertical plane and the system is configured to be mounted on a horizontal surface. In the embodiment on the right, the impactor is configured to rotate in a horizontal plane. [Figure 19] FIG. 10 illustrates a robotic arm removing a selectively removable cover from the impactor and rotating the impactor to a sampling position. [Figure 20] A diagram of the rotor mechanism with five impactors positioned on it. [Figure 21] 1 is a diagram of a device for a user to remove and replace a selectively removable cover of an impactor with one hand, the device may have a magnet configured to magnetically engage with a magnet on the selectively removable cover of the impactor. [Figure 22] 11-15 is a diagram of a robotic sampling system according to one embodiment of the present disclosure. The system may include some or all of the features of the embodiment of FIGS. 11-15, and further, the system may be mounted on a mobile robotic platform. [Figure 23] 1 is a diagram of a method and system for robotic sampling with a robotic sampling system including a mobile robotic platform. The illustrated system and method includes autonomously receiving an unused impactor from an impactor dispensing station, navigating to a sampling location for sampling with the impactor, navigating to an incubator station, and incubating the impactor with the incubator station, all without direct human intervention. [Figure 24] FIG. 1 illustrates one embodiment of navigating to a sampling location, docking with an enclosure, and collecting one or more samples from inside the enclosure.

[0035]

[0058] Description of chemical compounds and nomenclature Generally, the terms and phrases used herein have their art-recognized meanings, which can be found by reference to standard texts, journal sources, and contexts known to those skilled in the art. The following definitions are provided to clarify their specific use in the context of the present invention.

[0036]

[0059] "Particle" refers to small objects often considered contaminants. A particle can be any substance generated by the action of friction, for example, when two surfaces come into mechanical contact and mechanical movement is present. A particle can be composed of aggregates of materials such as dust, dirt, smoke, ash, water, soot, metals, 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 having sizes on the order of 0.1 to 20 μm. Biological particles include, for example, viable biological particles that can reproduce upon incubation in a growth medium. Particles can refer to small objects that absorb or scatter light and are therefore detectable by optical particle counters. As used herein, "particle" is intended to exclude individual atoms or molecules of a carrier fluid, such as gases present in air (e.g., oxygen molecules, nitrogen molecules, argon molecules, etc.) or process gases. Some embodiments of the present invention are capable of sampling, collecting, detecting, sizing, and / or counting particles, including aggregates of material having sizes of 50 nm, 100 nm, 1 μm or greater, or 10 μm or greater. Particular 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.

[0037]

[0060] The phrase "sampling particles" broadly refers to the collection of particles in a fluid stream, for example, from an environment being monitored. Sampling in this context includes the movement of particles in the fluid stream to an impact surface, such as a surface receiving a growth medium. Alternatively, sampling can refer to passing particles in a fluid through a particle analysis region, for example, for optical detection and / or characterization. Sampling can refer to the collection of particles having one or more preselected characteristics, such as size (e.g., cross-sectional dimension, such as diameter or effective diameter), particle type (biological or nonbiological, viable or nonviable, etc.), or particle composition. Sampling can optionally include analysis of the collected particles, for example, by subsequent optical, image, or visual analysis. Sampling can optionally include the growth of viable biological particles for the sample by an incubation process involving a growth medium. A sampler refers to a device for sampling particles.

[0038]

[0061] "Impactor" refers to a device for sampling particles. In some embodiments, the impactor comprises a sample head including one or more intake openings for sampling a particle-containing fluid stream, whereby at least a portion of the particles are directed to an impaction surface, such as a receiving surface of a growth medium (e.g., agar, broth, or other medium) or a substrate such as a filter, for collection. The impactor of some embodiments effects a change in direction of the flow after passing through the intake opening, and particles having a preselected characteristic (e.g., size greater than a threshold) do not change direction and are therefore received by the impaction surface.

[0039]

[0062] The phrase "detecting particles" broadly refers to sensing the presence of, identifying, counting, and / or characterizing particles, including characterizing particles with respect to size dimensions such as effective diameter. In some embodiments, detecting particles refers to counting particles. In some embodiments, detecting particles refers to characterizing and / or measuring physical properties of particles, such as effective diameter, cross-sectional dimension, shape, size, aerodynamic size, or any combination thereof. In some embodiments, detecting particles occurs in a flowing fluid, such as a gas, having a volumetric flow rate selected over a range of 0.05 CFM to 10 CFM, optionally 0.1 CFM to 5 CFM in some applications, and optionally 0.5 CFM to 2 CFM in some applications. In some embodiments, detecting particles occurs in a flowing fluid, such as a liquid, having a volumetric flow rate selected over a range of 1 to 1000 mL / min.

[0040]

[0063] "Flow direction" refers to the axis parallel to the direction in which the majority of the fluid is moving when the fluid is flowing. For fluid flowing through a straight flow cell, the flow direction is parallel to the path taken by the majority of the fluid. For fluid flowing through a curved flow cell, the flow direction can be considered to be tangential to the path taken by the majority of the fluid.

[0041]

[0064] "Fluid communication" refers to an arrangement of two or more objects such that a fluid can be transported to, through, or from one object to another. For example, in some embodiments, two objects are in fluid communication with each other if a fluid flow path is directly between them. In some embodiments, two objects are in fluid communication with each other if a fluid flow path is indirectly between them, such as by including one or more other objects or flow paths between them. For example, in one embodiment, the following components of a particle impactor are in fluid communication with each other: one or more intake openings, impact surfaces, fluid outlets, flow restrictions, pressure sensors, and flow generating devices. In one embodiment, two objects present in a body of fluid are not necessarily in fluid communication with each other unless fluid from the first object is drawn to, through, and / or via the second object, such as along a flow path.

[0042]

[0065] "Flow rate" refers to the amount of fluid flowing past a designated point or through a designated area, such as through an intake opening or fluid outlet of a particle impactor. In one embodiment, flow rate refers to mass flow rate, i.e., the mass of fluid flowing past a designated point or through a designated area. In one embodiment, flow rate is volumetric flow rate, i.e., the volume of fluid flowing past a designated point or through a designated area.

[0043]

[0066] "Operably connected," "operably coupled," "operably connected," and "operably coupled" refer to a configuration of elements in which the action or reaction of one element affects another element so as to maintain the functionality of each element. The connection may be by direct physical contact between the elements. The connection may be indirect, with another element indirectly connecting the operably connected elements. The term also refers to two or more functionally related components that are coupled to each other for the flow of electrical current and / or data signals. This coupling of two or more components may be a wired and / or wireless connection. Two or more components so coupled via a wired and / or wireless connection may be in close proximity to each other (e.g., in the same space or the same housing), or the two or more components may be separated by a distance in physical space (e.g., in different buildings).

[0044]

[0067] The term "pose" refers to the combination of (i) the location of an object in three-dimensional space (e.g., x, y, z coordinates relative to a reference point) and (ii) the orientation of the object relative to the direction of Earth's gravity (e.g., an object may have a reference surface that is oriented vertically so that the surface is parallel to the direction of Earth's gravity).

[0045]

[0068] The term "sampling orientation" refers to the orientation and location of an impactor, which is predetermined and configured to facilitate repeatable, location-specific collection of biological particles by the impactor. In one embodiment, the sampling orientation can be such that the impactor's impact surface is substantially horizontal. In one embodiment, multiple impactors can be disposed on a rotor mechanism configured to rotate the rotor, and therefore the impactors, about a substantially horizontal axis of rotation, and the sampling orientation corresponds to (i) the impactor being located at the highest point on the vertically oriented circle that the impactor traverses as it rotates about the horizontal axis of rotation, and (ii) the impactor's impact surface being substantially horizontal. In one embodiment, multiple impactors may be arranged on a rotor mechanism configured to rotate the rotor, and therefore the impactors, about a substantially vertical axis of rotation, and the sampling orientation corresponds to (i) the impactors being located at predetermined points on a horizontally oriented circle that the impactors follow as they rotate about the vertical axis of rotation, and (ii) the impact surfaces of the impactors being substantially horizontal.

[0046]

[0069] The term "substantially horizontal" refers to an orientation that is horizontal to within a predetermined angle. In one embodiment, substantially horizontal refers to an orientation that is less than 45 degrees from horizontal. In one embodiment, substantially horizontal refers to an orientation that is less than 35 degrees from horizontal. In one embodiment, substantially horizontal refers to an orientation that is less than 25 degrees from horizontal. In one embodiment, substantially horizontal refers to an orientation that is less than 15 degrees from horizontal. In one embodiment, substantially horizontal refers to an orientation that is less than 10 degrees from horizontal. In one embodiment, substantially horizontal refers to an orientation that is less than 5 degrees from horizontal. In one embodiment, substantially horizontal refers to an orientation that is less than 2 degrees from horizontal. In one embodiment, substantially horizontal refers to an orientation that is less than 1 degree from horizontal.

[0047]

[0070] The term "substantially vertical" refers to an orientation that is vertical to within a predetermined angle. In one embodiment, substantially vertical refers to an orientation that is less than 45 degrees from vertical. In one embodiment, substantially vertical refers to an orientation that is less than 35 degrees from vertical. In one embodiment, substantially vertical refers to an orientation that is less than 25 degrees from vertical. In one embodiment, substantially vertical refers to an orientation that is less than 15 degrees from vertical. In one embodiment, substantially vertical refers to an orientation that is less than 10 degrees from vertical. In one embodiment, substantially vertical refers to an orientation that is less than 5 degrees from vertical. In one embodiment, substantially vertical refers to an orientation that is less than 2 degrees from vertical. In one embodiment, substantially vertical refers to an orientation that is less than 1 degree from vertical.

[0048]

[0071] The term "rest position" refers to an orientation and location of the impactor where at least one of the following is true: (i) the impact surface of the impactor is not substantially horizontal, and / or (ii) the location of the impactor does not correspond to a predetermined sampling location. DETAILED DESCRIPTION OF THE INVENTION

[0049]

[0072] In the following description, numerous specific details of the devices, device components, and methods of the present invention are set forth in order to provide a thorough explanation of the precise nature of the invention. However, it will be understood by those skilled in the art that the present invention may be practiced without these specific details.

[0050]

[0073] Human presence, actions and intervention within the cleanroom are considered to be the greatest source of contamination risk.

[0051]

[0074] In one embodiment, the present system and method addresses this risk by using an impactor that will be at the sampling point pre-loaded into a system command or sampling tool configured to perform the following steps:

[0052]

[0075] I. Remove the impactor cover. The system command or sampling tool will hold the impactor cap, thereby allowing sampling.

[0053]

[0076] II. Place the impactor with the agar or other medium at the sampling point.

[0054]

[0077] III. Initiate active or passive sampling.

[0055]

[0078] IV. At a predetermined time and / or on command of the system or sampling equipment, the cover is reapplied to the impactor and a new impactor enters the cycle indicated in the previous point.

[0056]

[0079] Thus, in some embodiments, the system may provide essentially continuous (ie, continuous except for the time required to switch between impactors) autonomous sampling through the sequential use of multiple impactors.

[0057]

[0080] The systems and methods of the present invention provide several advantages, including:

[0058]

[0081] I. The device minimizes the risk of cleanroom contamination by replacing the primary source of contamination (human contact).

[0059]

[0082] II. Process automation cancels out human error and makes the process itself more uniform and repeatable.

[0060]

[0083] III. Microbiological monitoring, which can be continuous or sequential, ensures greater time coverage of the production process.

[0061] Example 1 - Robotic sampling system having a substantially horizontal axis of rotation and configured to be mounted on a vertical surface

[0084] 1A and 1B provide top and side views, respectively, of a robotic sampling system. The illustrated robotic sampling system 100 includes impactors 110A, 110B, and 110C, optionally single-use and / or disposable impactors, operatively connected to a rotor 120 configured to rotate about a central rotational axis 130. Rotation of the rotor 120 rotates the impactors 110A, 110B, and 110C, e.g., from a rest position to a sampling position. In the embodiment shown in FIGS. 1A and 1B, impactor 110A is in a sampling position in fluid communication with the environment under monitoring, and a flow of sample, air, other gases, particles, etc. (shown schematically as arrow 140) is provided to impactor 110A, while impactors 110B and 110C are in a rest position, e.g., a closed position. Considering the orientation of the central rotation axis 130, the robotic sampling system 100 is characterized as having a substantially horizontal axis of rotation. In one embodiment, the robotic sampling system 100 is disposed within or in fluid communication with an enclosure.

[0062]

[0085] Rotation of rotor 120 about central rotational axis 130 moves impactors 110A, 110B, and 110C along an arcuate path, e.g., along at least a portion of the circumference of a circle. In some embodiments, rotation allows impactors 110A, 110B, and 110C to assume sampling orientations that are substantially at the same sampling location (shown in FIG. 1A as the location of moving impactor 110A), but sampling at different times. In this manner, robotic sampling system 100 is capable of sequential and / or continuous sampling.

[0063]

[0086] In some embodiments, the sampling position includes being open with the cover removed, or being closed but with the cover removable. The sampling position is achieved to allow sampling of a stream of air and / or other gas under specific sampling conditions, such as for a selected time and / or a selected duration. In some embodiments, the rest position is a closed configuration, such as when the cover is in place. In some embodiments, the rest position corresponds to a pre-sampling state or a post-sampling state, such as when the impactor is in a closed configuration.

[0064]

[0087] 1A and 1B, impactors 110A, 110B, and 110C are single-use and / or disposable impactors. In some embodiments, impactors 110A, 110B, and 110C each independently comprise: (i) a sampling head with one or more intake openings for sampling the stream of air and / or other gases within the enclosure; (ii) an impactor base containing a growth medium for receiving particles from the stream of air and / or other gases, the growth medium having an impaction surface for receiving particles from the stream of air and / or other gases; (iii) a selectively removable cover for covering the one or more intake openings; and (iv) an outlet for discharging the stream of air and / or other gases.

[0065]

[0088] 2A-2I provide a schematic sequence illustrating the operation of a first embodiment of a robotic sampling system 100. The illustrated robotic sampling system 100 is provided within an enclosure 200, such as a sterile enclosure, a restricted access barrier system (RABS), or a positive pressure isolator system.

[0066]

[0089] FIG. 2A illustrates the robotic sampling system 100 prior to sampling, with each of the impactors 110A, 110B, and 110C engaging a removable cover to prevent sampling of particles in gases from the enclosure, such as air, process gas, and / or sterilant within the enclosure 200, and exposure of the growth medium to the particles. As shown in FIG. 2A, the robotic arm 300 is oriented so as not to physically contact any of the impactors 110A, 110B, and 110C. The system 100 further includes an isokinetic sampling probe 380 for counting non-viable particles. The probe 380 may be in communication with an optical particle counter (not shown). Thus, in some embodiments, the system 100 functions to count both viable and non-viable particles.

[0067]

[0090] FIG. 2B shows the robotic sampling system 100 at the start of operation, with the robotic arm 300 engaging the removable cover 115A of the impactor 110A, for example, by establishing a magnetic coupling between the removable cover 115A and the robotic arm 300.

[0068]

[0091] FIG. 2C shows the robotic sampling system 100 during cover removal, where the robotic arm 300 removes the cover 115A of the impactor 110A by lifting the cover 115A from the sampler head of the impactor 110A.

[0069]

[0092] 2D shows the robotic sampling system 100 during rotation, where rotation of the rotor 120 about the central rotation axis 130 moves the impactors 110A, 110B, and 110C along an arcuate path. As shown in FIG. 2D, the impactor 110A is rotated away from the rotating arm 300.

[0070]

[0093] FIG. 2D shows the robotic sampling system 100 after rotation, where rotation of the rotor 120 about the central rotation axis 130 has moved the impactor 110A to the sampling position, and 110B and 110C are in the rest position.

[0071]

[0094] 2E1 and 2E2 show the robotic sampling system 100 during fluid operation, in which a gas, such as air, process gas, and / or sterilant, from an enclosure (shown schematically as arrow 140) is supplied to the impactor 110A, for example, by generating a fluid flow through the impactor 110A, and at least a portion of the particles in the gas sample are sampled and contact the growth medium contained by the impactor 110A.

[0072]

[0095] FIG. 2F shows the robotic sampling system 100 after sampling, in which gases, such as air, process gases and / or sterilants, from the enclosure are no longer supplied to the impactor 110A, for example, by turning off fluid actuation and / or providing a removable cover to the impactor 110A.

[0073]

[0096] 2G shows the robotic sampling system 100 in rotation, where rotation of the rotor 120 about the central rotation axis 130 moves the impactors 110A, 110B, and 110C along an arcuate path. As shown in FIG. 2G, the impactor 110A is being rotated in a direction toward the rotating arm 300.

[0074]

[0097] FIG. 2G shows the robotic sampling system 100 after rotation, with the impactor 110A moved into position to receive the removable cover 115A.

[0075]

[0098] FIG. 2I shows the robotic sampling system 100 when the cover is replaced, and the robotic arm 300 presents the removable cover 115A to the impactor 110A, where the removable cover seals the impactor, such as by magnetic engagement between the removable cover and the sampler head.

[0076]

[0099] In some embodiments, the sample flow (e.g., 140) into impactors 110A, 110B, and / or 110C can be non-laminar. Under certain sampling conditions, for example, there can be a steep air velocity gradient on either side of the sampling head slit and / or opening along the flow axis. In some embodiments, the thickness of the sampling head slit along the flow axis is insufficient to provide a flow path that allows stable laminar flow to occur within the slit or opening, even when the Reynolds number is within the laminar flow region, because it may take a certain time / distance for stable laminar flow to form. However, the present robotic control system is compatible with other impactors and conditions, including pseudo-laminar and substantially laminar flow, e.g., flow characterized by a Reynolds number within the laminar flow region and / or a minimal velocity gradient along the flow axis.

[0077]

[0100] Figures 3A and 3B provide schematic diagrams of an impactor useful in the present systems and methods. Figure 3A is an exploded perspective view of particle impactor 1000, and Figure 2 is an exploded side view of particle impactor 1000. As shown in these figures, particle impactor 1000 comprises a sampling head 1200, a selectively removable cover 1100, and an impactor base 1300. Sampling head 1200 includes a sampling head magnet 1250 secured to the underside of sampling head 1200. Selectively removable cover 1100 includes a first cover magnet 1155 and a second cover magnet 1150 secured to the underside of cover 1100 and spaced apart by a spacer. Sampling head magnet 1250 engages second cover magnet 1150 to secure cover 1100 to the impactor. The sampling head 1200 and the selectively removable cover 1100 are engaged by a compressible sealing member 1110. The impactor 1000 is configured to compress the compressible sealing member 1110 by magnetic forces between the sampling head magnet 1250 and the second cover magnet 1150. The sampling head 1200 and impactor base 1300 are engaged by the compressible sealing member 1210. The first cover magnet 1155 may be configured to engage a robotic device, such as a robotic manipulator system.

[0078]

[0101] The sampling head 1200 includes a plurality of intake openings 1220 for sampling a particle-containing fluid stream. The impactor base 1300 includes an outlet 1320 and an impaction surface 1350. During operation, a gas stream is directed through the intake openings 1220 of the sampling head 1100, where it is accelerated toward the impaction surface 1350 and exits through the outlet 1320, which causes the gas to make a sudden change of direction. Due to their momentum, particles entrained in the gas stream are unable to make the sudden change of direction and impact the impaction surface 1350.

[0079]

[0102] In an embodiment, the impact surface 1350 comprises a receiving surface for a growth medium, such as agar, provided within the impactor base 1300. For example, viable biological particles collected on the impact surface can then be grown and evaluated to provide an analysis of the composition of the sampled fluid stream. For collection of biological particles on the impact surface, control of the distance between the intake opening 1220 and the impact surface 1350 is important. For example, if the distance is too large, the particles can navigate the fluid path sufficiently to avoid impact with the impact surface 1350. However, if the distance is too small, the particles may impact the impact surface 1350 with sufficient force to render the particles non-viable and therefore non-reproducible.

[0080]

[0103] Figure 3C shows a perspective view of the selectively removable cover 1100. Figure 3D shows a bottom view of the selectively removable cover 1100. Figure 3E shows a cross-sectional view of the selectively removable cover 1100. The selectively removable cover 1100 includes a first cover magnet 1155 and a second cover magnet 1150 secured to a central underside of the cover 1100 and separated by a spacer 1158. The first cover magnet 1155 can be configured to engage with a magnetic engagement mechanism of a robotic arm to remove the removable cover 1100 from the sampling head 1100 and / or replace the removable cover 1100 onto the sampling head 1100.

[0081]

[0104] The selectively removable cover 1100 also includes an O-ring groove 1120 on the underside of the cover 1100 proximal to the outer edge. The O-ring groove 1120 is configured to receive the O-ring 1110. A second cover magnet 1150 magnetically engages the sampling head magnet 1250 to compress the O-ring 1110. Thus, the cover 1100 can form an airtight seal with the sampling head 1200.

[0082] Example 2 - Robotic sampling system having a substantially horizontal axis of rotation and configured to be mounted through a vertical wall

[0105] 4-8, a second embodiment of a robotic sampling system 400 is shown. The robotic sampling system 400 may be configured to be mounted through the wall 330 of the enclosure 200. The system 400 includes multiple impactors 700. Each impactor 700 includes a sampling head 710, a selectively removable cover 720, and an impactor base 1300. The system 400 may further include a robotic arm, such as that shown in FIGS. 10-15. The robotic arm of the system 400 may be mounted through the wall 330. The sampling head 710 includes a lever 730 configured to facilitate removal of the selectively removable cover 720 by the robotic arm 390. The lever 730 includes a groove 735 configured to engage with a gripping element 392 of the robotic arm 390. The gripping element 392 may include a magnet 391 disposed therein. Additionally or alternatively, gripping element 392 may include a fork-like structure. For example, gripping element 392 may include a pair of tines configured to engage groove 735, one tine on each side of lever 730.

[0083]

[0106] The sampling head 710 and the selectively removable cover 720 are engaged by a compressible sealing member 1110. The impactor 700 is configured to compress the compressible sealing member 1110 by a friction fit between the sampling head 710 and the selectively removable cover 720. The sampling head 710 and the impactor base 1300 are engaged by a compressible sealing member 1210.

[0084]

[0107] The sampling head 710 includes a plurality of intake openings 1220 for sampling a particle-laden fluid stream. The impactor base 1300 includes an outlet 1320 and an impaction surface 1350. During operation, a gas stream is directed through the intake openings 1220 of the sampling head 710, where it is accelerated toward the impaction surface 1350 and exits through the outlet 1320, which causes the gas to make a sudden change of direction. Due to their momentum, particles entrained in the gas stream are unable to make the sudden change of direction and impact the impaction surface 1350.

[0085]

[0108] In an embodiment, the impact surface 1350 comprises a receiving surface for a growth medium, such as agar, provided within the impactor base 1300. For example, viable biological particles collected on the impact surface can then be grown and evaluated to provide an analysis of the composition of the sampled fluid stream. For collection of biological particles on the impact surface, control of the distance between the intake opening 1220 and the impact surface 1350 is important. For example, if the distance is too large, the particles can navigate the fluid path sufficiently to avoid impact with the impact surface 1350. However, if the distance is too small, the particles may impact the impact surface 1350 with sufficient force to render the particles non-viable and therefore non-reproducible.

[0086]

[0109] System 400 further includes a vacuum port 330 configured to connect to a vacuum source, and a power and control signal connector 340. As shown in Figure 4, system 400 can be mounted through wall 330 such that impactor 700 is within the enclosure, while vacuum port 330 and power and control signal connector 340 are accessible on the other side of wall 330 in non-sterile environment 250.

[0087]

[0110] The selectively removable cover 720 also includes an O-ring groove 1120 on the underside of the cover 1100 proximal to the outer edge. The O-ring groove 1120 is configured to receive an O-ring 1110. The selectively removable cover 720 engages with the sampling head 710 to compress the O-ring 1110. Thus, the cover 720 can form an airtight seal with the sampling head 720.

[0088]

[0111] System 400 further includes rotor 120. Rotation of rotor 120 rotates impactors 700 (e.g., 700A, 700B, 700C) from a rest position to a sampling position, similar to that described above with respect to system 100. In Figures 4 and 5, impactor 700A is in a sampling position and impactors 700B and 700C are in a rest position. Rotor 120 includes supports 320, 350 for holding impactor 700 in place.

[0089]

[0112] 7, the process of loading impactors 700 into the system is shown. The outlet 1320 of the impactor base of each impactor is inserted into its own receiving socket 122 in the rotor base plate 121 of the rotor 120 (e.g., impactor 700A is inserted into receiving socket 122A). As can be seen, for example, when impactor 700A is rotated into the sampling position, the outlet 1320 of impactor 700A aligns with the vacuum port 330. Thus, when each impactor is rotated into place, it can thereby be in fluid communication with the vacuum port 330.

[0090] Example 3 - Robotic sampling system having a substantially horizontal axis of rotation and configured to be mounted on a horizontal surface

[0113] 10-15 illustrate a third embodiment of a robotic sampling system 500. System 400 has many components and features similar to systems 400 and 100 described above. System 500 is configured with a base mount 510 for mounting to a horizontal surface. System 500 includes a probe 380 for sampling non-viable particles. System 500 also includes a robotic arm 390 having a gripping element 392. As previously described, each impactor 700 may include a lever 730 disposed on a selectively removable cover 720. Lever 730 may include a groove 735 configured to engage with the gripping element 392 of the robotic arm 390. Additionally or alternatively, lever 730 may include a magnet 731 configured to engage with the magnet 391 of the robotic arm 390.

[0091]

[0114] 12-15, the process of removing the selectively removable cover and rotating the impactor from the rest position to the sampling position is shown. First, as shown in FIG. 12, a gripping element of the robotic arm can engage a groove in the lever. Then, as shown in FIGS. 13-14, the robotic arm can rotate to peel the selectively removable cover off the impactor and expose the impact surface to the environment within the enclosure. Finally, as shown in FIG. 15, the rotor rotates the impactor to the sampling position, thereby placing the impactor in selective communication with the vacuum system, as described above.

[0092] Example 4 - Robotic sampling system having a substantially vertical axis of rotation and configured to be mounted on a horizontal surface

[0115] 16, a fourth embodiment of a system for robotic sampling is shown. The illustrated system 600 includes a plate holder 331, multiple impactors 700, an isokinetic probe 380, and a robotic arm 390. The impactors 700 are held in place by impactor holding members 410.

[0093]

[0116] During operation, the plate holder 331 rotates horizontally about its center, where the fixed isokinetic probe 380 is also positioned to sample non-viable or viable particles. As described above with respect to other embodiments, the outlet of the impactor base of each impactor is inserted into its own receiving socket in the plate holder 331. When the impactor is rotated to the sampling position, the impactor outlet aligns with the vacuum port in the plate holder. Thus, when each impactor is rotated into place, it can thereby be in fluid communication with the vacuum port. Furthermore, as described above, the gripping element of the robotic arm 390 can engage with a groove in the lever of the impactor 700. The robotic arm can then rotate to selectively peel the removable cover off the impactor and expose the impact surface to the environment within the enclosure.

[0094] Example 5 - Robot Arm

[0117] 17, an example of a robotic arm for removing and replacing a selectively removable cover is shown. In the illustrated embodiment, the robotic arm includes a gripping element comprising a fork-like structure.

[0095] Example 6 - Separate sampling channels for viable and non-viable particles

[0118] Referring to Figure 18, two different embodiments of sampling paths for viable and non-viable particles are shown. In the embodiment on the left, the impactor is configured to rotate in a vertical plane and the system is configured to be mounted on a horizontal surface. In the embodiment on the right, the impactor is configured to rotate in a horizontal plane.

[0096] Example 7 - Method of operating a robotic sampling system having a substantially horizontal axis of rotation and configured to be mounted on a horizontal surface

[0119] 19, a sequence of steps is shown for removing a selectively removable cover from an impactor by a robotic arm and rotating the impactor to a sampling position. In the illustrated embodiment, the rotor mechanism rotates counterclockwise to the cover removal position. The selectively removable cover is then removed by the robotic arm. The rotor mechanism then rotates the impactor to the sampling position and sampling begins.

[0097] Example 8 - Rotor mechanism with five impactors placed on it

[0120] 20, a diagram of a rotor mechanism having five impactors disposed thereon is shown. While the illustrated embodiment has five impactors, the present disclosure expressly contemplates a robotic sampling system configured for any number of impactors.

[0098] Example 9 - Device for manually operating a selectively removable cover

[0121] 21, there is shown a diagram of an apparatus for a user to one-handedly remove and replace a selectively removable cover of an impactor. The apparatus may have a magnet configured to magnetically engage with a magnet on the selectively removable cover of the impactor.

[0099] Example 10 - Mobile Robot Platform

[0122] 22, a diagram of a robotic sampling system including a mobile robotic platform is shown. The system may include one or more of the features described above. Additionally, the mobile robotic platform may include a navigation system and a robotic transport system. In some embodiments, the combination of the navigation system and the robotic transport system may enable autonomous movement in a clean room environment. The robotic sampling system may include one or more robotic arms for manipulating the impactor.

[0100] Example 11 - Navigation of a mobile robotic platform

[0123] 23-24, diagrams of the navigation of a mobile robotic platform throughout a manufacturing facility are shown. In the illustrated embodiment, the mobile robotic platform can transport the robotic sampling system to an impactor dispensing station, where the robotic sampling system receives an unused impactor from the impactor dispensing station. The mobile robotic platform can then transport the robotic sampling system to a sampling location for sampling. The system can selectively remove a removable cover from the impactor, rotate the impactor to a sampling position, and begin sampling. After one or more samples are collected by the impactor, the system can proceed to an incubator station and move the used impactor to the incubator station. The incubator station can then incubate the impactor to determine the presence of biological particles.

[0101] 24, a mobile robotic platform can transport a robotic sampling system to an enclosure. The mobile robotic platform can then dock with the enclosure by inserting the robotic sampling system into the enclosure through a port designed to accept the robotic sampling system. The sampling system can then take another sample from inside the enclosure while the mobile robotic platform remains outside the enclosure.

[0102] INCORPORATION-BY-REFERENCE AND MODIFICATION STATEMENT

[0124] All references cited throughout this application, e.g., patent literature, including issued or allowed patents or their equivalents, patent application publications, and non-patent literature, or other source materials, are hereby incorporated by reference in their entirety, as if each reference were individually incorporated by reference to the extent that it is at least partially consistent with the disclosure in this application (e.g., a partially conflicting reference is incorporated by reference except for the partially conflicting portion of the reference).

[0103]

[0125] The terms and expressions used herein are used as terms of description and not as terms of limitation, 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 modifications are possible within the scope of the invention as defined by the appended claims. Thus, while the present invention has been specifically disclosed in terms of preferred embodiments, exemplary embodiments, and optional features, it should be understood that modifications and variations of the concepts disclosed herein may be made by those skilled in the art, and that such modifications and variations are considered to be within the scope of the invention as defined by the appended claims. The specific embodiments provided herein are examples of useful embodiments of the invention, and as will be apparent to those skilled in the art, the invention may be practiced using numerous variations of the devices, device components, and method steps described herein. As will be apparent to those skilled in the art, the methods and devices useful therefor may include numerous optional compositions and processing elements and steps.

[0104]

[0126] When a group of substituents is disclosed herein, it is understood that all individual members and all subgroups of that group are separately disclosed. When Markush groups or other groupings are used herein, all individual members of the group, and all possible combinations and subcombinations of groups, are intended to be included individually in the disclosure.

[0105]

[0127] It should be noted that, as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, a reference to a "cell" includes a plurality of such cells and equivalents thereof known to those skilled in the art, and so forth. Similarly, the terms "a" (or "an"), "one or more," and "at least one" can be used interchangeably herein. It should also be noted that the terms "comprising," "including," and "having" can be used interchangeably. The phrase "as defined in any of claims XX-YY" (XX and YY refer to claim numbers) is intended to provide multiple dependent claims in the alternative and, in some embodiments, can be substituted for the phrase "as defined in any one of claims XX-YY."

[0106]

[0128] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are now described. Nothing herein should be construed as an admission that the invention is not entitled to antedate such disclosure by virtue of prior invention.

[0107]

[0129] Any combination of the components described or illustrated herein can be used to practice the invention unless otherwise stated.

[0108]

[0130] Whenever a range is given in the specification, e.g., a range of integers, 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 within the disclosure. As used herein, ranges specifically include the values ​​provided as the endpoints of the range. As used herein, ranges specifically include all integer values ​​within the range. For example, a range of 1 to 100 specifically includes the endpoints of 1 and 100. Of course, any subranges or individual values ​​within a range or subrange included in the description herein may be excluded from the claims herein.

[0109]

[0131] All patents and publications mentioned in this specification are indicative of the level of skill of those skilled in the art to which this invention pertains. The references cited herein are incorporated by reference in their entirety to indicate the state of the art as of their publication or filing date, and it is intended that this information may be used herein, if necessary, to exclude certain embodiments that are in the prior art. For example, if a composition of matter is claimed, it should be understood that compounds known and available in the art prior to Applicant's invention, including compounds for which enabling disclosure is provided in the references cited herein, are not intended to be included in the composition of matter claims herein.

[0110]

[0132] As used herein, "comprising" is synonymous with "including," "including," or "characterized by," and is inclusive or open-ended, not excluding additional, unrecited elements or method steps. As used herein, "consisting of" excludes any element, step, or ingredient not specified in the claimed element. As used herein, "consisting essentially of" does not exclude materials or steps that do not materially affect the basic and novel characteristics of the claim. In each case, any of the terms "comprising," "consisting essentially of," and "consisting of" may be substituted for either of the other two terms. The inventions illustratively described herein may be practiced in the absence of any element or elements, or limitation or limitations not specifically disclosed herein.

[0111]

[0133] Those skilled in the art will understand that starting materials, biological materials, reagents, synthetic methods, purification methods, analytical methods, assay methods, and biological methods other than those specifically exemplified can be used in the practice of the present invention without resort to undue experimentation. All art-known functional equivalents of any such materials and methods are intended to be encompassed by this invention. The terms and expressions that have been used are used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions to exclude any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention as defined in the claims. Thus, while the present invention has been specifically disclosed in terms of preferred embodiments and optional features, it should be understood that modifications and variations of the concepts disclosed herein may be made by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention as defined by the appended claims.

Claims

1. 1. A robotic sampling system for sampling particles in an enclosure, comprising: a sampling head comprising one or more intake openings for sampling the stream of air and / or other gas within the enclosure; an impactor base including a growth medium for receiving particles from the stream of air and / or other gas, the growth medium having an impact surface for receiving particles from the stream of air and / or other gas; a selectively removable cover for covering said one or more intake openings; an outlet for discharging said stream of air and / or other gas; an impactor for holding the growth medium, comprising: a robotic manipulator system configured to rotate the impactor from a rest position to a sampling position; A robotic sampling system comprising:

2. The robotic sampling system of claim 1 , comprising a plurality of impactors.

3. The robotic sampling system of claim 1 or 2, wherein the selectively removable cover includes a magnet configured to magnetically engage the robotic manipulator system.

4. The robotic sampling system of claim 3 , wherein the robotic manipulator system is configured to remove the selectively removable cover with the magnet.

5. 5. The robotic sampling system of claim 3 or 4, wherein the robotic manipulator system is configured to replace the selectively removable cover by means of the magnet.

6. The robotic sampling system of any one of claims 1 to 5, comprising a robotic arm, the robotic arm including a magnetic engagement mechanism for engaging the magnetism of the selectively removable cover.

7. The robotic sampling system of claim 6 , wherein the magnetic engagement mechanism includes an electromagnet.

8. 8. The robotic sampling system of claim 1, configured to robotically remove a used impactor from the robotic manipulator system and robotically replace the used impactor with a new impactor.

9. the robotic manipulator system comprises: (i) rotating a first impactor of the plurality of impactors from a sampling orientation to a rest orientation; (ii) rotating a second impactor of the plurality of impactors from a rest position to a sampling position; The robotic sampling system of any one of claims 2 to 8, configured to:

10. 10. The robotic sampling system of claim 9, wherein the robotic manipulator system is configured to perform steps (i) and (ii) simultaneously.

11. 11. The robotic sampling system of claim 9 or 10, wherein the sampling orientation of the first impactor is the same as the sampling orientation of the second impactor.

12. The robotic sampling system of any one of claims 1 to 11, wherein the system is configured to rotate the impactor along a trajectory that follows a portion of a complete circle or a complete circle.

13. 13. The robotic sampling system of claim 12, wherein the circle has a diameter selected from the range of 2 cm to 1000 cm.

14. 14. The robotic sampling system of claim 12 or 13, wherein when the robotic manipulator system rotates the impactor from a rest position to a sampling position, the impactor has a trajectory characterized by an arc having an arc length selected from 10° to 180°.

15. 15. The robotic sampling system of claim 14, wherein the robotic manipulator is configured to provide a trajectory for a sampler having a tolerance for repeatability of the arc length of less than 30% of the arc length.

16. The robotic sampling system of any preceding claim, wherein the rotation is about a horizontal axis.

17. The robotic sampling system of any preceding claim, wherein the rotation is about a vertical axis.

18. The robotic sampling system of any preceding claim, wherein the impact surface is oriented horizontally when the impactor is in the sampling position.

19. The robotic sampling system of any preceding claim, wherein the impact surface is oriented vertically when the impactor is in the rest position.

20. A robotic sampling system according to any preceding claim, comprising a flow system for flowing fluid through a particle detection device.

21. The robotic sampling system of claim 20 , wherein the flow system is coupled to the outlet of the sampling impactor.

22. 22. The robotic sampling system of claim 2, comprising a rotor mechanism configured to engage the plurality of impactors disposed thereon, the impactors being oriented about an axis of rotation of the rotor mechanism, and the rotor mechanism configured to rotate about the axis of rotation.

23. 23. The robotic sampling system of claim 22, wherein the axis of rotation is substantially horizontal.

24. 24. The robotic sampling system of claim 22 or 23, wherein the axis of rotation is within 10 degrees of horizontal.

25. The robotic sampling system of any one of claims 22 to 24, wherein the axis of rotation is within 5 degrees of horizontal.

26. each impactor having a bottom surface opposite the impact surface; each impactor is positioned on the rotor mechanism such that the bottom surface of each impactor faces toward the axis of rotation; The robotic sampling system according to any one of claims 22 to 25.

27. 27. The robotic sampling system of claim 22, wherein when the impactor is rotated to the sampling orientation, the impact surface of the impactor is substantially horizontal and facing upwards, and the impactor is located at the highest point on the rotational path followed by the rotor mechanism.

28. 28. A robotic sampling system according to any one of claims 22 to 27, wherein when the impactor is rotated to a rest position, the impact surface of the impactor is not substantially horizontal and / or does not face upwards.

29. 23. The robotic sampling system of claim 22, wherein the axis of rotation is substantially vertical.

30. 30. The robotic sampling system of claim 22 or 29, wherein the axis of rotation is within 10 degrees of vertical.

31. 31. The robotic sampling system of any one of claims 22 or 29-30, wherein the axis of rotation is within 5 degrees of vertical.

32. the impact surface of each impactor remains substantially horizontal when rotated by the rotor mechanism from a rest position to a sampling position; 32. The robotic sampling system of claim 22 or any one of claims 29 to 31.

33. 33. The robotic sampling system of claim 22 or any one of claims 29 to 32, wherein the plurality of impactors are arranged on the rotor mechanism such that each impactor follows the same rotational path, the rotational path defining a substantially horizontal plane.

34. A robotic sampling system according to any one of claims 2 to 33, wherein each impactor is positioned equidistant from the axis of rotation.

35. A robotic sampling system according to any preceding claim, comprising a status indicator to indicate whether the system is in sampling mode.

36. The robotic sampling system of any one of claims 1 to 35, wherein the impactor is a single-use or disposable device.

37. 37. The robotic sampling system of any one of claims 1 to 36, wherein the impactor base, the sampling head, or both are optically transparent to allow visualization, optical detection, or imaging of particles, including viable biological particles, in the growth medium without physically accessing the growth medium.

38. The robotic sampling system of any one of claims 1 to 37, wherein the sampling head and the impactor base engage via a substantially airtight seal.

39. 39. The robotic sampling system of any one of claims 1 to 38, wherein the stream of air flowing through the impactor has a flow rate selected from 2 lpm to 500 lpm.

40. 40. The robotic sampling system of any one of claims 1 to 39, wherein the enclosure is a sterile enclosure, a restricted access barrier system (RABS), or a positive pressure isolator system.

41. The robotic sampling system of any one of claims 1 to 40, comprising a mobile robotic platform, the robotic manipulator system being mounted on the mobile robotic platform.

42. the mobile robotic platform: A navigation system, Robot transport system 42. The robotic sampling system of claim 41, wherein the navigation system is configured to guide the robotic transport system to move the robotic sampling system from a sampling location to an incubator station.

43. the mobile robotic platform: A navigation system, Robot transport system 43. The robotic sampling system of claim 41 or 42, wherein the navigation system is configured to guide the robotic transport system from an impactor dispensing station to a sampling location.

44. 1. A method for sampling particles in an enclosure, comprising: rotating the impactor from a rest orientation to a sampling orientation with a robotic manipulator system; removing a selectively removable cover covering one or more intake openings of the impactor; sampling a stream of air and / or other gas from within or from the enclosure with the impactor, said sampling comprising: Intake of said stream of air and / or other gas by a sampling head comprising said one or more intake openings; impacting particles from the stream of air and / or other gas onto an impact surface of a growth medium within an impactor base of the impactor; discharging the stream of air and / or other gas from the impactor through an outlet of the impactor; a sampling step, comprising: A method comprising:

45. 1. A method of controlling a robotic sampling system for sampling particles in an enclosure, comprising: providing a first command to a robotic manipulator system, the first command configured to cause the robotic manipulator system to rotate an impactor from a rest position to a sampling position; providing a second command to the robotic manipulator system, the second command configured to cause the robotic manipulator system to remove a selectively removable cover from the impactor; providing a third command to a fluid actuation system, the third command configured to cause the fluid actuation system to draw air and / or other gas from the enclosure into the impactor; A method comprising:

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