Fluid analysis device and method

Abstract

The fluid analysis apparatus (1) comprises a particle quantification device (4), a holder (6), a robot (3), a washing station (5), and a control unit (2). The particle quantification device (4) has a sensor unit (42) with a detection stick (421) to be placed in a fluid to detect particles in the fluid, and an evaluation unit (41). The holder (6) has a plurality of pedestals, each configured to receive a container in which a sample fluid is placed. The control unit (2) is connected to the particle quantification device (4) and the robot (3). The sensor unit (42) is mounted on the robot (3). The control unit (2) is configured to control the robot (3) to place the detection stick (421) into one of the sample fluids of each of the containers received in the base of the holder (6) one after the other, to drive the particle quantification device (4) to detect particles in the sample fluid, and to control the robot (3) to place the detection stick (421) into the washing station (5) after each detection of a particle in one of the sample fluids and before placing the detection stick (421) into the next one of the sample fluids.

Description

Technical Field

[0001] The present invention relates to a fluid analysis device and a method for analyzing a fluid. Such devices and methods may be used to analyze fluids, particularly to control the quality of fluids with respect to the presence of visible and sub-visible particles.

Background Art

[0002] In the context of fluid quality control, verification regarding the presence of particles is often involved. For example, in the development or manufacture of pharmaceutical fluids such as liquid parenteral drugs, it is typically required to ensure that the drug does not contain any particles that may cause undesirable side effects or a decrease in efficacy when administered.

[0003] Accordingly, certain devices are often used to identify particles in a liquid. Such devices include various techniques for identifying particles within a desired range, including sub-visible particles. For example, some devices apply optical methods based on either light scattering, light obscuration, or direct imaging. Typically, then, the device comprises a sensor equipped with a high-intensity light source such as a laser source or halogen light. The light source is used to provide a light beam to the liquid passing through the detection chamber to illuminate potentially present particles. When light scattering is used, the redirected light is detected by a photodetector. When light shielding or light obscuration is used, a loss of light is detected. The intensity of the scattered or shielded light is measured, and the particles are counted and tabulated into standardized counting bins.

[0004] To enable convenient access to the liquid inside the container, the sensors of such devices are often provided with a cuvette or a needle. Using such a cuvette or needle, the liquid or a sufficient amount of the liquid can be withdrawn from the container and sent to a suitable location accessible by the sensor.

[0005] The devices of the type described above enable the accurate identification of particles in a liquid such that these devices are generally used for quality control in the pharmaceutical industry and other industries. Further, such devices are accepted in standard procedures that are required to be applied to comply with the conditions defined by the job authority.

[0006] However, while known devices used for particle identification are accurate and widely accepted, these devices typically operate in a relatively inefficient manner, especially when a relatively large number of samples have to be analyzed. Moreover, when processing multiple samples, there is a significant risk of cross - contamination since cuvettes are successively placed into the sample liquid. More specifically, known devices typically operate by placing a container, such as a vial, containing the fluid to be analyzed, on a given platform of the device that is accessible by the cuvette of the sensor. The cuvette is then introduced into the liquid inside the vial and the liquid is examined for particles. The sensor data is transferred to a computing unit or evaluation unit of the device where the data is evaluated. After examining the liquid, the cuvette is lifted out of the liquid and the vial is removed from the platform. In a subsequent step, a subsequent vial is placed on the platform and the cuvette is introduced into the liquid of the vial.

[0007] Considering the above, there is a need for a system that enables the efficient and accurate analysis of multiple fluids with respect to the presence of particles. SUMMARY OF THE INVENTION

[0008] According to the present invention, the above - mentioned need is solved by a fluid analysis device as defined by the features of independent claim 1 and by a method for analyzing a fluid as defined by the features of independent claim 17. Preferred embodiments are the subject of the dependent claims.

[0009] In one aspect, the present invention is a fluid analysis device comprising a particle quantification device, a holder, a robot, a cleaning station, and a control unit. The particle quantification device has a sensor unit with a detection stick to be placed in the fluid for withdrawing the fluid and detecting particles in the fluid, and an evaluation unit. The holder has a plurality of pedestals each configured to receive a container in which a sample fluid is placed. Thus, the holder is configured to receive a plurality of sample fluids each placed in one of the containers received on one of the pedestals of the holder. The control unit is connected to the particle quantification device and to the robot. The sensor unit is mounted on the robot. The control unit is configured to control the robot to place the detection stick successively into one of the sample fluids of one of the containers received on the pedestal of the holder to drive the particle quantification device to detect particles in the sample fluid, and to control the robot to place the detection stick in the cleaning station after each has detected particles in one of the sample fluids and before placing the detection stick in the next of the sample fluids. In particular, the control unit can be configured to drive the particle quantification device to detect particles in the sample fluid by successively detecting particles in one of the sample fluids of the containers received on the pedestal of the holder. Thus, the control unit can be configured to place the detection stick in the cleaning station between detecting particles in two different sample fluids.

[0010] As used herein, the term "particle" relates to any undissolved entity or substance present in the sample fluid. Particles may particularly relate to fine particles other than air bubbles unintentionally present in the sample fluid and typically solid substances.

[0011] The particle quantification device can be any device suitable for quantifying or identifying particles in a desired size range in a fluid. Thus, the particles can be quantified by directly measuring the concentration of the particles in the fluid or by indirectly determining the concentration by measuring the amount of particles in a predetermined flow of the fluid. In addition, the particle quantification device can also measure further characteristics of the particles, such as size, shape, etc. Specifically, the particle quantification device can be a liquid particle counter such as the analytical device HIAC9703+ commercialized by Beckman Coulter, Inc. or a similar device. The particles detected and evaluated by the particle quantification device may or may not include sub-visible particles. Such a particle quantification device can optically identify the particles in the fluid. For example, the particle quantification device can apply light obscuration technology for identifying the particles.

[0012] The fluid analysis device can be configured in particular for use in quality control. For example, the fluid analysis device can be adapted to control the quality of a drug substance according to the requirements defined by the authorities applicable in pharmaceutical development and manufacturing. For example, the United States Pharmacopeia (USP) defines in its General Chapter <788> "Particulate Matter in Injections" the requirements to be applied for the investigation of injections and parenteral infusions for the method of sub-visible particles and for ensuring the quality of substances to be delivered by injection or infusion. Thus, the fluid analysis device can be used to control the quality of the fluid in accordance with USP <788>.

[0013] The container can be any storage container suitable for containing the sample fluid to be analyzed. The container can be, in particular, a vial, a test tube, a cartridge, etc. As used herein, the term "vial" can relate to a literal vial, i.e., a relatively small vessel or bottle, often used for storing pharmaceutical products or pharmaceuticals or drugs in liquid, powdered or encapsulated form. The vial can be made of a sterilizable material such as glass or a plastic such as polypropylene, for example. The vial typically includes a cover or cap that includes a sealing material such as a rubber stopper or a septum designed to be pierced for many applications.

[0014] The sensing stick can be a cuvette or a needle, more specifically, a hypodermic needle. Known particle quantification devices use a hypodermic needle as a sensing stick, which can also be advantageous for introduction into the container even in cases where the container is relatively small or has a relatively small opening. The sensing stick can be configured to aspirate or draw fluid into a sensing unit that detects particles. More specifically, through the sensing stick, a sample fluid or a sufficient amount of the sample fluid can be withdrawn from the container and sent to an appropriate location of a sensor unit capable of analyzing the presence of particles. Also, by withdrawing, the sensing stick can receive the liquid moving inside the sensor unit, which can be advantageous in many types of sensor technologies.

[0015] The cleaning station of the device according to the invention enables the sensor unit to be efficiently cleaned during the measurement of two consecutive sample fluids. This makes it possible to prevent cross-contamination between the sample fluids so as to ensure an appropriate quality of a single measurement result, and to avoid the situation where the sample fluid has to be disposed of after the particles have been detected. In particular, it can be advantageous when a relatively expensive sample fluid, such as a biological preparation, for example, a fluid having an antibody, is included and when the sample fluid can be further processed.

[0016] By having a robot that transports the detection stick of the sensor unit, it is possible to realize that physical detection is automatically performed. Thus, the analysis efficiency can be increased, especially when a relatively large number of sample fluids are involved. Therefore, the holder enables the exact location and orientation of the container to be determined in advance so that the robot can precisely position the detection stick inside the sample fluid.

[0017] Moreover, by providing a control unit and connecting the control unit to the robot and the particle quantification device, the entire process can be automatically executed so that the efficiency can be essentially increased. The connection between the control unit and the robot or the particle quantification device can be any suitable data communication connection. For example, the control unit can be connected to the robot and the particle quantification device via cables or wiring. A wireless connection is also possible. Furthermore, one or more suitable protocols and / or interfaces can be used to communicate with the robot and / or the particle quantification device. For example, the particle quantification device is typically provided with an interface for communication and includes a predetermined protocol for interaction. Such an interface and protocol can be used in the device according to the invention to establish a connection between the control unit and the particle quantification device.

[0018] The control unit may be or may include any suitable computing device such as a conventional computer. Thus, the term "computer" relates to any electronic data processing device or apparatus. The term can include a single device such as a server computer, a desktop computer, a laptop computer, a tablet, a smartphone, an embedded system, etc. The term may also relate to a combination of such devices such as a distributed system having components in different locations. Typically, a computer is composed of a plurality of components such as a central processing unit (CPU), a hard disk, a flash memory or the like, a permanent data storage having a random access memory (RAM), a read-only memory (ROM), a universal serial bus (USB), a local area network (LAN) adapter, a wireless LAN (WLAN) adapter, a communication adapter such as a Bluetooth adapter or the like, a user interface such as a keyboard, a touch screen, a mouse, a screen, a microphone, a loudspeaker or the like, and other components. Thus, a computer can be assembled into various embodiments of the above components and / or other components.

[0019] Configuring the control unit in accordance with the present invention can include executing a dedicated computer program on a computer to perform each task. Thus, the computer can be arranged to physically connect to the robot and the particle quantification device, to logically execute steps to evaluate and interact with the robot and the particle quantification device, and to give instructions to the robot and the particle quantification device. Giving instructions can include transmitting a data signal to the robot and / or the particle quantification device. These data signals can represent instructions that can be understood and implemented by the robot and / or the particle quantification device.

[0020] As described above, by equipping the fluid analysis device with a cleaning station and configuring the control unit to cause the robot to place the detection stick in the cleaning station after detecting particles in each sample fluid, it is possible to ensure that the detection stick is clean before being moved to the next sample fluid. In this way, cross-contamination between sample fluids can be prevented. For efficient cleaning of the sensor unit, the cleaning station can be a multi-element assembly. In particular, the cleaning station can have multiple components to provide the various tasks involved in cleaning the sensor unit.

[0021] Preferably, the cleaning station comprises a cleaning medium storage unit for storing a cleaning medium and a cleaning medium forwarder connected to the cleaning medium storage unit, a control unit is connected to the cleaning station, and after the particle quantification device has detected particles in one of the sample fluids in the container received on the pedestal of the holder and before the particle quantification device has detected particles in the other sample fluid in the container received on the pedestal of the holder, the cleaning medium forwarder is configured to drive the cleaning medium to wash away the sensor unit or in particular the detection stick of the sensor unit. As used herein, the term "wash away" may in particular relate to supplying the cleaning medium through the detection stick. The washing away may also include supplying the cleaning medium outside any component of the sensor unit, but supplying the cleaning medium through the detection stick may clearly be advantageous. The cleaning medium forwarder included herein may be any structure that enables the medium to be sent or advanced to wash away the sensor unit. In particular, in one advantageous variant, the cleaning medium forwarder can be embodied as a pump or can comprise a pump for actively advancing or sending the cleaning medium. Alternatively, in another advantageous variant, the cleaning medium forwarder can comprise a valve or a similar structure connected to a storage unit for storing the cleaning medium under pressure. Thus, in this variant, the cleaning medium forwarder can be embodied as a combination of a pressurized storage unit and a valve or a similar structure. Therefore, driving the valve or a similar structure makes it possible to control the cleaning medium flowing out of the storage unit. Providing the cleaning medium storage unit and the cleaning medium forwarder makes it possible to efficiently clean the sensor unit in an automated manner driven by the control unit.

[0022] The cleaning medium can be a solution or purified water such as ultrapure water or water for injection in particular. Alternatively or in addition, the cleaning medium may be or may contain ethanol or a similar substance or a reagent suitable for cleaning. As a result, the cleaning medium storage section can be a solution storage section, a pure water storage section, an ethanol storage section or another substance storage section. Advantageously, the control unit is configured to flush the sensor unit with the cleaning medium after detecting a sample fluid in one container and before detecting another sample fluid in the next container.

[0023] Accordingly, the cleaning station preferably has a cleaning pedestal where the detection stick is arranged when the sensor unit is flushed with the cleaning medium. While flushing the sensor unit, the cleaning medium can be discharged to the cleaning pedestal by the detection stick. The cleaning pedestal can be incorporated into the block or body of the cleaning station. Such a cleaning pedestal enables the detection stick to be efficiently and precisely positioned in an automated manner via a robot.

[0024] The cleaning station preferably comprises a cleaning medium cavity arranged to receive the cleaning medium after flushing the sensor unit. The cleaning medium cavity and the cleaning pedestal may be the same structure incorporated into the cleaning station or different structures.

[0025] Preferably, the cleaning pedestal and the cleaning medium cavity are in fluid communication such that the cleaning medium after flushing the sensor unit is supplied to the cleaning pedestal and transferred from the cleaning pedestal to the cleaning medium cavity. The fluid communication between the cleaning pedestal and the cleaning medium cavity can be established by an overflow structure arranged such that the cleaning medium flows from the cleaning pedestal to the cleaning medium cavity after filling the cleaning pedestal to a certain extent and before the cleaning medium exits the cleaning station.

[0026] The control unit is preferably configured to control a robot to place a sensing stick within a cleaning medium cavity to detect particles in the cleaning medium after flushing the sensor unit. Such a configuration enables ascertaining whether the cleaning medium is sufficiently clean to conclude that there are no particles within the sensor unit. Thus, the control unit can efficiently ensure that the sensor unit is clean before measuring any further sample fluid. More specifically, such a configuration enables using the particle quantification device itself to ascertain the cleanliness of the sensor unit and to prevent cross-contamination in an efficient and automated manner.

[0027] Accordingly, the control unit is preferably configured to control a robot to place the sensing stick into another one of the sample fluids in a container received on a pedestal of the holder when the amount of detected particles in the cleaning medium after flushing the sensor unit is lower than a predetermined threshold. The other one of the containers can in particular be the next one in a series of containers. Predetermining the threshold and ensuring that it is not exceeded enables efficiently ensuring sufficient cleanliness of the sensor unit and that no limit amount of residual particles are within the sensor unit.

[0028] The control unit is even more preferably configured to drive a cleaning medium forwarder to flush the sensor unit with the cleaning medium when the amount of detected particles in the cleaning medium after flushing the sensor unit is higher than a predetermined threshold. Here, the sensor unit may be re-flushed to achieve an appropriate cleanliness. The sensing stick can be repositioned on a cleaning pedestal during the re-flushing.

[0029] The cleaning station preferably comprises a drying coupler, and the control unit is configured to control the robot to place the sensing stick into the drying coupler before placing the sensing stick into another one of the containers received on the pedestal of the holder in the sample fluid. The drying coupler can be any coupling structure that enables coupling the sensing stick to dry the sensor unit. For example, the drying coupler can be a drying cavity that can be provided with a gasket structure to enable a precise coupling of the sensing stick. By equipping the cleaning station with a drying coupler, it can be realized that the sensor unit is dried after being cleaned. In this way, it can be prevented that the cleaning medium contacts the sample fluid that may adversely affect the measurement.

[0030] Accordingly, the cleaning station preferably comprises a vacuum generator connected to the control unit, and the control unit is configured to drive the vacuum generator to dry the sensor unit when the sensing stick is placed in the drying coupler. The vacuum generator can be any structure or component that enables applying a negative pressure to the drying coupler. For example, the vacuum generator can comprise a vacuum pump. Or, the vacuum generator can be equipped with a vacuum vessel coupled to the drying coupler via a controllable valve, for example. Such a vacuum generator enables sucking or drawing out the cleaning medium remaining outside the sensor unit after being rinsed. The vacuum generator enables efficient automated drying of the sensor unit after cleaning and before detecting particles in the subsequent sample fluid.

[0031] Preferably, the fluid analysis device is provided with a shaker, and the holder is arranged on the shaker so as to be moved by the shaker. By swinging the holder and the container together with it, it is possible to realize that the particles in the sample fluid are kept suspended. In other words, it is possible to prevent the particles from settling so that they can no longer be detected by the sensor unit. Keeping the particles in suspension may be a requirement of relevant standard specifications such as USP No. 788. In particular, since a relatively large amount of sample fluid may sometimes be automatically processed by the fluid analysis device without any human intervention over a fairly long period of time, the shaker can ensure that the particles are accurately detected in the sample fluid of all relevant containers.

[0032] Therefore, the control unit is preferably configured to drive the shaker when the detection stick is not placed in the sample fluid of any container that the pedestal of the holder is to receive. Such a configuration enables precise detection of the particles in the sample fluid even against any obstacles induced by the movement of swinging the relevant container.

[0033] Preferably, the robot is a linear robot embodied to move the sensor unit along the horizontal x-axis and the vertical z-axis. Advantageously, the robot is embodied to additionally move the sensor unit along the horizontal y-axis. Such a linear robot enables efficient and accurate movement of the detection stick or the entire sensor unit between the container and the cleaning station. Moreover, such a linear robot is typically relatively robust and causes relatively little maintenance effort.

[0034] Preferably, the fluid analysis device comprises a sample loop installed between the sensor unit of the particle quantification device and the evaluation unit of the particle quantification device. The term "sample loop" in this context may relate to any structure that enables increasing the distance or fluid path between the control unit and the evaluation unit of the particle quantification device or other components. In this way, it is possible to ensure that the fluid sample does not come into contact with the evaluation unit and / or other components. The sample loop can be embodied as a tube that enlarges the flow path after the sensor unit. In order to achieve a substantial increase without requiring a relatively large space, the tube of the sample loop can be wound or arranged similarly. In the case where the particle quantification device has a pump or a similar element to draw the sample fluid to the sensor unit via the detection stick, the sample loop can essentially reduce the risk of the sample fluid coming into contact with the pump or a similar element, and thus the risk of cross-contamination occurring between multiple sample fluids.

[0035] Preferably, the fluid analysis device comprises a sample fluid drawer that is fluidly connected to the detection stick of the sensor unit. Thus, the sample fluid drawer can be embodied as a pump. Such a pump enables controlled pumping of the sample fluid into the system and in particular into the sensor unit so that accurate and safe pumping is possible. Also, such a pump can be made to pump the sample fluid in the reverse direction if required. Alternatively, the sample fluid drawer can be any other pressure regulating system. For example, the sample fluid drawer is included by the particle quantification device. Advantageously, the fluid connection between the sample fluid drawer and the detection stick of the sensor unit passes through the sample loop. In this way, the sample loop may be arranged to be fluidly connected between the sample fluid drawer and the detection stick of the sensor unit.

[0036] Accordingly, the fluid connection structure between the sample fluid drawer and the sensing stick of the sensor unit is preferably at least partially filled with a transmission medium. The fluid connection structure can be a tube or a similar conduit that allows liquid movement and / or pressure transmission.

[0037] In an advantageous embodiment, the transmission medium is a liquid that is compressed relatively little during the pumping of the sample fluid. For example, the transmission medium may be purified water. A gas such as air can be placed between the transmission medium and the sample fluid to prevent contact between the sample fluid and the transmission medium. By providing the transmission medium, pressurized transmission can be achieved, enabling more accurate pumping of the sample fluid. For example, the effects caused by changing the gas volume between the sample fluid drawer and the sensing stick can be essentially reduced. In particular, having a transmission medium can be particularly advantageous when the path between the sample fluid drawer and the sensing stick is relatively large, such as when a sample loop is provided.

[0038] In another advantageous embodiment, the transmission medium is a low-reactivity gas such as an inert gas. For example, the transmission medium can be nitrogen or a similar gas. Such a transmission medium makes it possible to ensure that no residue is found in the path between the sample fluid drawer and the sensing stick, such as in a sample loop. More specifically, the transmission medium makes it possible to prevent contamination of the pumped sample fluid.

[0039] In another aspect, the present invention is a method for analyzing a fluid, comprising: i) obtaining a plurality of containers each filled with a sample fluid to be analyzed; ii) automatically arranging, by a robot, a detection stick of a sensor unit of a particle quantification device in one of the sample fluids of the plurality of containers; iii) automatically detecting, by the sensor unit of the particle quantification device, particles in one of the sample fluids; iv) automatically arranging, by the robot, the detection stick of the sensor unit of the particle quantification device in a cleaning station; v) cleaning the detection stick of the sensor unit of the particle quantification device arranged in the cleaning station; and vi) repeating steps ii) to v) for each of the other ones of the sample fluids of the plurality of containers in sequence.

[0040] Although the steps of the method according to the present invention are numbered above, this numbering should not be understood as limiting the method to a particular order. Rather, the recited steps may be performed in a different order or sequence.

[0041] The method according to the present invention and its preferred embodiments described below make it possible to realize the effects and advantages of the fluid analysis device and its preferred embodiments described above.

[0042] Preferably, step v) includes the step of flushing the sensor unit with a cleaning medium by a cleaning medium forwarder. Accordingly, the cleaning station preferably has a cleaning pedestal where the detection stick is arranged when the sensor unit is flushed with the cleaning medium.

[0043] The cleaning medium is preferably collected after flushing the sensor unit. Thus, the sensor unit of the particle quantification device preferably automatically detects the particles in the collected cleaning medium. Thus, step vi) is preferably executed when the amount of detected particles in the collected cleaning medium is below a predetermined threshold. Step v) is preferably re-executed when the amount of detected particles in the collected cleaning medium is above a predetermined threshold.

[0044] Preferably, step v) includes the step of drying the sensor unit. Thus, the step of drying the sensor unit preferably includes the step of the vacuum generator of the cleaning station applying a vacuum to the sensor unit.

[0045] Preferably, the method includes the step of rocking a plurality of containers in step iii), in step iv) and in step v). Such a rocking step is preferably applied by a shaker that can operate and be controlled automatically.

[0046] The fluid analysis device according to the present invention and the method according to the present invention will be described in more detail hereinafter with reference to exemplary embodiments and the accompanying drawings.

Brief Description of the Drawings

[0047]

Figure 1

Figure 2

Figure 3

Modes for Carrying Out the Invention

[0048] In the following description, certain terms are used for convenience and are not intended to limit the present invention. The terms "right," "left," "up," "down," "under," and "above" refer to directions in the figures. The terminology includes the explicitly recited terms as well as their derivatives and terms having similar meanings. Also, terms indicating spatial relationships such as "beneath," "below," "lower," "above," "upper," "proximal," "distal," etc. may be used to describe the relationship of one element or configuration to another element or configuration as illustrated in the figures. These terms indicating spatial relationships are intended to encompass different positions and orientations of the device in use or in operation in addition to the positions and orientations shown in the figures. For example, if the device in the figure is turned over, an element described as "below" or "beneath" another element or configuration should then be "above" or "over" the other element or configuration. Thus, the exemplary term "below" can encompass both positions and orientations above and below. The device may otherwise be oriented (rotated 90 degrees or otherwise), and the descriptions indicating spatial relationships used herein can be interpreted accordingly. Similarly, descriptions of movement along and around various axes include various particular device positions and orientations.

[0049] To avoid repeating the figures and descriptions of various aspects and exemplary embodiments, it should be understood that many features are common to many aspects and embodiments. The omission of an aspect from the description or figures does not mean that the above aspect is lost from the embodiments incorporating this aspect. Instead, the above aspect may be omitted for clarity and to avoid redundant description. In this context, the following applies to the remainder of this description: To clarify the drawings, if a figure includes reference numerals that are not described in the directly relevant part of the description, refer to the previous or subsequent description items. Further, for reasons of clarity, if not all configurations of a component are given reference numerals in the drawings, refer to other drawings showing the same component. The same numbers in two or more figures represent the same or similar elements.

[0050] FIG. 1 shows an embodiment of a fluid analysis apparatus 1 according to the present invention. The fluid analysis apparatus 1 includes a liquid particle counter 4 as a particle quantification device, a linear robot 3, a holder 6, a shaker 7, a cleaning station 5, and a control unit 2.

[0051] The control unit 2 is a computer that executes dedicated software for configuring a computer that executes various tasks to automatically process the analysis of a plurality of sample fluids.

[0052] The liquid particle counter 4 includes an evaluation station 41 and a sensor unit 42. The liquid particle counter 4 is configured to apply light obscuration technology to identify particles in a fluid. For example, the liquid particle counter may be an analytical device HIAC9703+ commercialized by Beckman Coulter, Inc. The evaluation station 41 and the sensor unit 42 are interconnected by wiring such that a sensor signal can be transmitted from the sensor unit 42 to the evaluation station 41 that can analyze and further process the sensor signal. The evaluation station 41 has an interface through which the evaluation station is connected to the control unit 2 via a data wiring. Accordingly, the control unit 2 is configured to communicate with the evaluation station 41 in accordance with a protocol predefined by the liquid particle counter 4 or its manufacturer by dedicated software.

[0053] The linear robot 3 has an x-arm 31, a y-arm 32, and a z-arm 33. The y-arm 32 is mounted on the x-arm 31 such that the y-arm 32 can linearly move back and forth along the horizontal axis x, that is, left and right in FIG. 1. Further, the z-arm 33 is mounted on the y-arm 32 such that the z-arm 33 can linearly move back and forth along the horizontal axis y, that is, up and down in FIG. 1. Finally, the sensor unit 42 is mounted on the z-arm 33 such that the sensor unit 42 can linearly move back and forth along the vertical axis z, that is, out of the plane shown in FIG. 1. The linear robot 3 has an interface through which the linear robot 3 is connected to the control unit 2 via a data wiring. Accordingly, the control unit 2 is configured to communicate with the linear robot 3 in accordance with a protocol predefined by the linear robot or its manufacturer by dedicated software. In particular, the control unit 2 is configured to move the sensor unit 42 to any desired position using the linear robot 3.

[0054] The holder 6 has a plurality of pedestals each configured to receive a vial as a container in which a sample fluid is placed. The plurality of vials arranged on the pedestals of the holder contain different fluid samples to be analyzed for the presence of visible and sub - visible matter in quality control. The holder 6 is placed on the shaker 7 such that when the shaker 7 is driven, the shaker 7 moves the holder 6. Accordingly, the vials installed in the holder 6 are likewise moved or oscillated so that ultimately the particles inside the sample fluid continue to be suspended or dispersed in the sample fluid. In this way, it is possible to realize that the particles can be reliably identified by the sensor unit 42. To drive the shaker 7, the shaker 7 is connected to the control unit 2 via wiring. The control unit 2 is configured by dedicated software to drive and stop the shaker 7 when desired.

[0055] The cleaning station 5 has a pure water storage unit 53 as a cleaning medium storage unit filled with ultrapure water, a storage and cleaning solution storage unit 54, and a cleaning pump 52 as a cleaning medium forwarder. The cleaning pump 52 is in fluid communication with the pure water storage unit 53, the storage and cleaning solution storage unit 54, and the sensor unit 42. The cleaning pump 52 is further connected to the control unit 2 via wiring. The control unit 2 is configured by dedicated software to drive and stop the cleaning pump 52 as desired.

[0056] The cleaning station 5 includes a cleaning body 51 and a vacuum pump 55 as a vacuum generator. The cleaning body 51 is equipped with a cleaning pedestal 511, a cleaning medium cavity 512 that is in fluid connection with the cleaning pedestal 511 using an overflow structure 513, and a drying coupler 514 connected to the vacuum pump 55. The vacuum pump 55 is connected to the control unit 2 via wiring. The control unit 2 is configured by dedicated software to drive and stop the vacuum pump 55 as desired. The cleaning medium cavity 512 is in fluid connection with the waste container 8 of the fluid analysis device 1.

[0057] In FIG. 2, the fluid analysis device 1 is shown from the side. Thus, it can be seen that the sensor unit 42 is equipped with an injection needle 421 as a sensing stick. When the sensor unit 42 is vertically displaced by the z-arm 33 of the linear robot 3, i.e., up and down in FIG. 2, and horizontally displaced by the x-arm 31 and the y-arm 32, the injection needle 421 does not move within the sensor unit 42 so that it is moved in conjunction with the rest of the sensor unit 42. In this way, the injection needle 421 may be positioned by the control unit 2 so as to be installed at any location necessary for processing the sample fluid to confirm particles.

[0058] As can be seen in FIG. 2, the cleaning pedestal 511 and the cleaning medium cavity 512 are sized to conveniently receive the injection needle 421. The overflow structure 513 connects the cleaning pedestal 511 to the cleaning medium cavity 512 such that when the cleaning pedestal 511 is filled with fluid to a certain level, the fluid overflows into the cleaning medium cavity 512. The drying coupler 514 is sized to snugly receive the injection needle 421. The drying coupler 514 is further equipped with a gasket structure to achieve tightness. In particular, the drying coupler 514 is arranged such that when the injection needle 421 is placed within the drying coupler 514 and the vacuum pump 55 applies a vacuum, the sensor unit 42 is set to a negative pressure via the injection needle 421.

[0059] FIG. 3 shows a flow scheme for illustrating the logical interrelationships of the components of the fluid analysis device 1. Thus, it can be seen that the pure water storage section 53 and the storage and cleaning solution storage section 54 are connected to the cleaning pump 52 via the three-way cleaning medium valve 56 of the cleaning station 5. The control unit 2 is configured to set the cleaning medium valve 56 to determine whether the cleaning pump 52 sends the ultrapure water from the pure water storage section 53 or the solution from the storage and cleaning solution storage section 54 when driven by dedicated software.

[0060] The liquid particle counter 4 is equipped with a sensor pump 43 as a sample fluid drawer, and the sensor pump 43 is connected to the sensor unit 42 via the three-way sensor valve 92 and the sample loop 91 of the fluid analyzer 1. The sample loop 91 is embodied by a tube helix and connects the detection stick 421 to the sensor valve 92. The control unit 2 is configured by dedicated software to set the sensor valve 92 to determine whether the sensor unit 42 is connected to the sensor pump 43 to draw out the sample fluid or ultrapure water to be measured by the sensor unit 42 through the injection needle 421, or to the cleaning pump 52 to supply ultrapure water or a solution through the sample loop 91 and the sensor unit 42.

[0061] The sensor pump 43 is further connected to the waste container 8 so that all the fluid sent by the sensor pump 43 can be collected in the waste container 8. As can be further seen in FIG. 3, the overflow structure 513 of the cleaning body 51 has an inclined surface that can ensure that the fluid can only flow from the cleaning pedestal 511 to the cleaning medium cavity 512 and cannot flow back.

[0062] The fluid analyzer 1 operates in a method for analyzing a fluid according to the present invention as follows:

[0063] The holder 6 is provided with a plurality of vials each filled with the sample fluid to be analyzed. The control unit 2 controls the linear robot 3 to automatically place the injection needle 421 into one of the sample fluids in the plurality of vials. The control unit 2 sets the sensor valve 92 to open the sensor pump 43 towards the sensor unit 42. The control unit 2 drives the sensor pump 43 so that the sample fluid is drawn through the injection needle 421 into the sensor unit 42 that automatically detects particles in the sample fluid. The sensor signal is transmitted from the sensor unit 42 to the evaluation station 41 where the sensor signal is evaluated. The control unit 2 then stops the sensor pump 43 and controls the linear robot 3 to automatically place the injection needle 421 onto the cleaning pedestal 511 of the cleaning station 5.

[0064] The control unit 2 sets the sensor valve 92 to open the cleaning pump 52 towards the sensor unit 42. The control unit 2 further sets the cleaning medium valve 56 to open the cleaning pump 52 towards the pure water storage unit 53. The control unit 2 drives the cleaning pump 52 so that the sample loop 91 and the sensor unit 42 are flushed with ultrapure water sent to the cleaning pedestal 511. Once the cleaning pedestal 511 is filled up to the overflow structure 513, the ultrapure water flows into the cleaning medium cavity 512.

[0065] After flushing the sensor unit 42, the control unit 2 controls the linear robot 3 to place the injection needle 421 inside the cleaning medium cavity 512. Next, the control unit 2 appropriately sets the sensor valve 92 and operates the sensor pump 43 so that the injection needle 421 draws out ultrapure water from the cleaning medium cavity 512. The drawn-out ultrapure water is here analyzed for the presence of particles by the liquid particle counter 4 in the same way as the sample fluid.

[0066] In the case where the amount or concentration of particles identified by the liquid particle counter 4 is higher than a predetermined threshold value, flushing the sensor unit 42 as described above is repeated. Once the amount or concentration of particles identified by the liquid particle counter 4 becomes lower than the predetermined threshold value, the control unit 2 controls the linear robot to change the location of the injection needle 421 into the drying coupler 514. Next, the control unit 2 drives the vacuum pump 55 that creates a negative pressure inside the sensor unit 42 and the sample loop 91. In this way, the remaining ultrapure water is removed or drawn out. Here, the control unit 2 controls the linear robot to place the injection needle 421 into the next sample fluid of a plurality of vials.

[0067] The overall cycle of analyzing the sample fluid and cleaning the system is repeated by the control unit 2 until the sample fluid in all vials has been analyzed. Thus, the control unit 2 drives the shaker 7 whenever the injection needle 421 is not installed in any vial. After the sample fluid in all vials has been analyzed, the control unit controls the system to be finally cleaned with the solution contained in the storage and cleaning solution reservoir 54.

[0068] This specification and the accompanying drawings, which illustrate aspects and embodiments of the invention, are not to be taken as limiting the scope of the claims that define the protected invention. In other words, while the invention has been described and illustrated in detail in the drawings and the foregoing description, such description and illustration are to be considered illustrative or exemplary and not restrictive. Various mechanical, compositional, structural, electrical, and operational changes may be made without departing from the spirit and scope of this specification and the claims. In some instances, well-known circuits, structures, and techniques have not been shown in detail so as not to obscure the invention. Thus, it will be understood that changes and modifications may be made by those skilled in the art within the scope of the appended claims and the spirit thereof. In particular, the invention covers further embodiments in any combination of features from the different embodiments described above and below.

[0069] The disclosure also covers all additional features shown separately in the figures, which may not be described in the previous or following description. Also, a single alternative of an embodiment described in the figures and the specification, as well as a single alternative of its features, may be waived from the subject matter of the invention or the disclosed subject matter. The present disclosure includes the subject matter consisting of the features defined in the claims or exemplary embodiments and the subject matter having those features.

[0070] Moreover, in the claims, the term "comprising" does not exclude other elements or steps, and the indefinite articles "a" or "an" do not exclude a plurality. A single unit or step may perform the functions of several features recited in the claims. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that combinations of these measures cannot be used advantageously. Terms such as "essentially", "about", "approximately", etc. with an attribute or a value in particular define exactly the above attribute or exactly the above value respectively. In the context of a given value or range of values that can be calculated, the term "about" refers to a value or range that is, for example, within 20%, within 10%, within 5%, or within 2% of the given value or range. Components described as being coupled or connected may be directly coupled electrically or mechanically, or they may be indirectly coupled through one or more intermediate components. All reference signs in the claims should not be construed as limiting the scope.

Claims

1. A particle quantification device (4), comprising a sensor unit (42) with a detection stick (421) arranged in the fluid for detecting particles in the fluid, and an evaluation unit (41); A holder (6) having a plurality of pedestals each configured to receive a container in which a sample fluid is disposed; A robot (3); A cleaning station (5); And a control unit (2) connected to the particle quantification device (4) and the robot (3), A fluid analysis device (1), wherein The sensor unit (42) is mounted on the robot (3), The control unit (2) is configured to: Control the robot (3) to place the detection stick (421) into one of the sample fluids of each container received by the pedestal of the holder (6) in sequence; Drive the particle quantification device (4) to detect particles in the sample fluid; and Control the robot (3) to place the detection stick (421) in the cleaning station (5) after each detection of particles in one of the sample fluids and before placing the detection stick (421) into the next one of the sample fluids. Composed of Fluid analysis device (1).

2. The cleaning station (5) comprises a cleaning medium storage part (53) for storing a cleaning medium and a cleaning medium forwarder (52) connected to the cleaning medium storage part (53). The control unit (2) is connected to the cleaning station (5). After the particle quantification device (4) detects particles in the sample fluid of one of the containers received by the pedestal of the holder (6) and before the particle quantification device (4) detects particles in the sample fluid of another one of the containers received by the pedestal of the holder (6), the control unit (2) is configured to drive the cleaning medium forwarder (52) to wash the sensor unit (42) with the cleaning medium. The fluid analysis device (1) according to Claim 1.

3. The cleaning medium is supplied to a cleaning pedestal (511) after flushing the sensor unit (42), and the cleaning pedestal (511) and the cleaning medium cavity (512) are in fluid communication such that the cleaning medium is transferred from the cleaning pedestal (511) to the cleaning medium cavity (512). The fluid analysis device (1) according to claim 2.

4. The control unit (2) is configured to control the robot (3) to place the detection stick (421) in the cleaning medium cavity (512) in order to detect particles in the cleaning medium after flushing the sensor unit (42). The fluid analysis device (1) according to claim 3.

5. The cleaning station (5) includes a drying coupler (514), and the control unit (2) controls the robot (3) to place the detection stick (421) in the drying coupler (514) before placing the detection stick (421) in one of the other sample fluids of the containers received on the pedestal of the holder (6). Optionally, The cleaning station (5) includes a vacuum generator (55) connected to the control unit (2), and the control unit (2) is configured to drive the vacuum generator (55) to dry the sensor unit (42) when the detection stick (421) is placed in the drying coupler (514). The fluid analysis device (1) according to any one of claims 1 to 4.

6. Comprising a shaker (7), The holder (6) is placed on the shaker (7) so as to be moved by the shaker (7). The fluid analysis device (1) according to any one of claims 1 to 5.

7. The robot (3) is a linear robot (3) embodied to move the sensor unit (42) along a horizontal x-axis and a vertical z-axis. The fluid analysis device (1) according to any one of claims 1 to 6.

8. Comprising a sample loop (91) installed between the sensor unit (42) of the particle quantification device (4) and the evaluation unit (41) of the particle quantification device (4). The fluid analysis device (1) according to any one of claims 1 to 7.

9. The fluid analysis device (1) according to any one of claims 1 to 8, comprising a sample fluid drawer (43) in fluid connection with the detection stick (421) of the sensor unit (42).

10. A method for analyzing a fluid, comprising: i) obtaining a plurality of containers each filled with a sample fluid to be analyzed; ii) automatically placing, by a robot (3), a detection stick (421) of a sensor unit (42) of a particle quantification device (4) into one of the sample fluids in the plurality of containers; iii) automatically detecting, by the sensor unit (42) of the particle quantification device (4), particles in the one of the sample fluids; iv) automatically placing, by the robot (3), the detection stick (421) of the sensor unit (42) of the particle quantification device (4) into a cleaning station (5); v) cleaning the detection stick (421) of the sensor unit (42) of the particle quantification device (4) disposed in the cleaning station (5); vi) repeating steps ii) to v) for each of the other ones of the samples in the plurality of containers in sequence A method comprising:

11. The method according to claim 10, wherein step v) includes flushing the sensor unit (42) with a cleaning medium by a cleaning medium forwarder (52).

12. The method according to claim 11, wherein the cleaning medium is collected after flushing the sensor unit (42). The method according to claim 11.

13. Step vi) is performed when the amount of detected particles in the collected cleaning medium is below a predetermined threshold, and / or Step v) is re-executed when the amount of the detected particles in the collected cleaning medium is above a predetermined threshold. The method according to claim 12.

14. Step v) includes drying the sensor unit (42). The method according to any one of claims 10 to 13.

15. The method according to any one of claims 10 to 14, including rocking the plurality of containers in steps iii), iv) and v).

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