In-line addition of automated nanoparticle reference materials

Abstract

Systems and methods are described for automatically handling and maintaining a nanoparticle standard solution in a substantially homogeneous state by controlled introduction into a fluid sample. Embodiments of the system include a stirrer configured to mix a nanoparticle standard solution in a container to provide a mixed nanoparticle standard having a substantially homogeneous distribution of nanoparticles; and a fluid preparation system fluidly coupled to the container to receive the mixed nanoparticle standard and direct the mixed nanoparticle standard into a fluid sample stream for in-line mixing therewith.

Description

Technical Field

[0001] Cross - reference to related applications This application claims the benefit of 35 U.S.C.§119(e) of U.S. Provisional Application Serial No. 63 / 350,642, filed on June 9, 2022, entitled "AUTOMATED INLINE NANOPARTICLE STANDARD MATERIAL ADDITION", and the entire disclosure of this application is incorporated herein by reference.

Background Art

[0002] Inductively coupled plasma (ICP) mass spectrometry is an analytical technique commonly used for measuring trace element concentrations and isotope ratios in liquid samples. ICP mass spectrometry uses an electromagnetically generated, partially ionized argon plasma, the temperature of which reaches about 7000K. When a sample is introduced into the plasma, the high temperature causes the sample atoms to ionize or emit light. Since each chemical element produces a characteristic mass spectrum or emission spectrum, the elemental composition of the original sample can be determined by measuring this spectrum.

[0003] For analysis, a sample introduction system may be employed to introduce a liquid sample into an ICP mass spectrometer (e.g., inductively coupled plasma mass spectrometer (ICP / ICPMS), inductively coupled plasma atomic emission spectrometer (ICP - AES), etc.). For example, the sample introduction system can take an aliquot of a liquid sample from a container and then transport the aliquot to a nebulizer, converting it into a polydisperse aerosol suitable for ionization in the plasma by an ICP mass spectrometer. Thereafter, the aerosol is sorted in a spray chamber, and larger aerosol particles are removed. The aerosol exiting the spray chamber is introduced into an ICPMS or ICPAES device for analysis. Often, sample introduction is automated, and a large number of samples can be efficiently introduced into an ICP mass spectrometer.

Summary of the Invention

[0004] Systems and methods for the automated handling of a homogeneous nanoparticle standard solution and subsequent in-line introduction into a sample solution prior to analysis are described herein. Embodiments of the system include, but are not limited to, a stirrer configured to mix a nanoparticle standard solution within a container to provide a mixed nanoparticle standard having a substantially homogeneous distribution of nanoparticles; and a fluid preparation system fluidly coupled to the container and configured to receive the mixed nanoparticle standard, wherein the fluid preparation system includes a valve system and one or more pumps and is configured to deliver the mixed nanoparticle standard through the valve system, contact the mixed nanoparticle standard with a fluid sample stream to mix in-line with the fluid sample stream, and provide a mixed sample and nanoparticle standard solution prior to transferring the same to an analysis system.

[0005] Embodiments of the method include, but are not limited to, mixing a nanoparticle standard solution within a container via a stirrer to provide a mixed nanoparticle standard having a substantially homogeneous distribution of nanoparticles; transferring the mixed nanoparticle standard via a fluid line to a fluid preparation system including a valve system and one or more pumps; and contacting the mixed nanoparticle standard via one or more pumps with a fluid sample stream through the valve system to mix in-line with the fluid sample stream and provide a mixed sample and nanoparticle standard solution prior to transferring the same to an analysis system.

[0006] This summary is provided to introduce a selection of concepts in a simplified form that are further described below in the detailed description. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter. BRIEF DESCRIPTION OF THE DRAWINGS

[0007] The detailed description is set forth with reference to the accompanying drawings.

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

MODE FOR CARRYING OUT THE INVENTION

[0008] Overview The research on nanoparticles has grown to encompass applications from the medical industry to the environmental industry. Such applications can focus on the function of detecting nanoparticles (e.g., particles with a diameter less than 1000 nm) and calculating the size of the nanoparticles present in a sample. However, when analyzing spectrometric data, it is accompanied by many difficulties to determine what is a nanoparticle and what is not. For example, spectrometric data such as ICPMS data contains information related to the ionized sample and background interferences such as those resulting from the plasma gas introduced into the ICP torch, which may overlap with the data related to small nanoparticles. For example, as the size of the nanoparticles decreases, the spectroscopic analysis data of the nanoparticles begins to converge with the data related to the ion species generated by the ICP torch. This overlap and the issues related to removing background interferences while avoiding removing nanoparticle data lead to continuous problems in providing reliable data related to nanoparticles, including but not limited to the identification of nanoparticles, the determination of the number of nanoparticles, and the associated size distribution.

[0009] Nanoparticle reference materials or reference materials (RMs) can be used to determine the transport efficiency of samples that may contain nanoparticles and provide an opportunity to determine the nanoparticle concentration and nanoparticle size in the sample based on known reference materials. Examples of nanoparticle reference materials can include suspensions of gold nanoparticles provided in a liquid matrix, and the standard suspension contains nanoparticles with known concentrations and sizes or size distributions. The nanoparticle reference materials can vary between samples in terms of the material of the nanoparticles, the matrix of the nanoparticles, the concentration of the nanoparticles, the size of the nanoparticles, etc., or combinations thereof, and can vary according to the desired sample analysis.

[0010] Since many nanoparticle reference materials are available for sample analysis, various containers of nanoparticle reference materials may be idle while waiting to be used, and nanoparticles may precipitate within the containers. The sedimentation of nanoparticles can lead to local concentration differences within the container, which may adversely affect the concentration of the reference material. In that case, when withdrawing the amount of the reference material from the container, the concentration of nanoparticles may be significantly different from the concentration assumed to be the reference material. Although the container can be mixed before use, when multiple sample containers are waiting for analysis by an autosampler, the mixing operation may take time. For example, long-term mixing of nanoparticle standards may damage the nanoparticles and prevent batch mixing of multiple containers. Furthermore, nanoparticle reference samples cannot usually be pre-loaded into sample containers because many chemicals contained in the sample may dissolve or otherwise damage the nanoparticles in the reference sample (e.g., by directly introducing the reference sample into the sample container of the sample waiting for analysis) before being taken in by the autosampler probe, especially when a significant amount of time elapses between the introduction of the reference sample and the intake of the mixture of the sample and the reference sample by the autosampler, thus interfering with accurate analysis. Therefore, laboratory staff usually add the nanoparticle reference to the sample immediately before sample analysis to minimize the time the sample interacts with the nanoparticle reference. When analyzing multiple samples, laboratory staff must perform numerous operations to prepare the reference sample and the sample for analysis to avoid damaging the nanoparticle reference sample. As a result, the cost increases, and opportunities for errors occur multiple times (e.g., incorrect reference sample used for the particle sample, incorrect amount of the reference sample used, incorrect time for introducing the reference sample, etc.), making sample analysis inefficient.

[0011] Accordingly, in one aspect, the present disclosure relates to a system and method for automatically processing a homogeneous nanoparticle standard solution and then automatically introducing it in-line into a fluid sample at a specified time before analysis for introduction into one or more fluid samples. Embodiments of the system include a stirrer for mixing a nanoparticle standard container before drawing the volume of the homogenized nanoparticle standard into an isolated fluid path (e.g., via a pump or vacuum introduction) having an accurate volume. The system can include a pump system and a valve system, and while the sample is being sent to a sample analysis system (e.g., the nebulizer of an ICP analysis system), the nanoparticle standard is directed from the isolated fluid path into the sample stream and mixed with the sample. This system can automatically introduce a cleaning liquid into the fluid path used to transfer and separate the nanoparticle solution between samples to clean the fluid line before introducing different nanoparticle standards. A purge gas can be flowed through the cleaning liquid to remove trace amounts of the cleaning liquid in the fluid line and prevent mixing of the cleaning liquid with the subsequent nanoparticle standard (e.g., to avoid inaccurate dilution between them).

[0012] Implementation example Figures 1-7 show a system 100 for automatically processing and maintaining a nanoparticle standard solution in a substantially homogeneous state by controlled introduction into a fluid sample to prevent decomposition of the nanoparticles present in the nanoparticle standard solution. As used herein, the term "nanoparticle standard solution" encompasses all forms of solid or semi-solid nanoparticles present in a fluid matrix, including solid-liquid suspensions, solid-liquid solutions, and the like. System 100 generally includes a stirrer 102 that mixes one or more nanoparticle standard solutions 104 to provide a substantially uniform distribution of nanoparticles within each solution, and a fluid preparation system 106 that receives the mixed nanoparticle solutions 104 and one or more fluid samples 108 and prepares (prepares) a fluid sample and nanoparticle standard for introduction into an analysis system 110. Stirrer 102 includes, but is not limited to, a platform shaker, a rotary mixer, an ultrasonic mixer, a magnetic stirring mixer, a rocking mixer, or combinations thereof. Stirrer 102 can facilitate mixing of one or more containers holding nanoparticle standard solution 104 by using one or more stirring structures. For example, stirrer 102 includes a first mixer for mixing a single container or multiple containers holding the same or different nanoparticle standard solutions 104, a second mixer for mixing a single container or multiple containers holding the same or different nanoparticle standard solutions 104, and the like. When stirrer 102 includes multiple mixing structures, stirrer 102 can provide individual mixing of each container or group of containers. For example, stirrer 102 can mix a first container of nanoparticle standard solution 104 while leaving a second container of nanoparticle standard solution 104 in an idle state (e.g., unmixed). By leaving the second container of nanoparticle standard solution 104 in an idle state until it is needed for analysis, it is possible to prevent the nanoparticles from being decomposed into uncalibrated sizes / shapes due to stresses associated with nanoparticle mixing (e.g., due to collisions with the container, collisions with other nanoparticles, etc.). In embodiments, system 100 can include a cooling device such as a Peltier cooler for cooling one or more fluids passing through system 100.For example, the stirrer 102 includes a Peltier cooler and can maintain one or more of the nanoparticle standard solutions 104 at a temperature lower than the ambient temperature.

[0013] The fluid preparation system 106 may include a valve system 112 including one or more valves and a pump / vacuum system 114 including one or more pumps and / or one or more vacuum sources to facilitate the automatic transport of fluid through the system 100. An example of the fluid preparation system 106 will be further described with reference to FIGS. 2 to 7. The analysis system 110 receives fluid from the fluid preparation system 106 and analyzes and determines one or more components of the fluid, such as the concentration to be analyzed, the size of the nanoparticles, and the concentration of the nanoparticles. For example, the analysis system 110 includes, but is not limited to, one or more ICP spectroscopic instruments such as ICPMS instruments, and related sample preparation instruments such as nebulizers and ICP torches.

[0014] Referring to FIGS. 2-7, an example of system 100 is shown, which transitions between states (e.g., through the operation of valve system 112 and pump / vacuum system 114) to facilitate the handling of nanoparticle standard solution 104 and enable automatic in-line introduction into fluid sample 108. System 100 includes two nanoparticle standard containers (shown as 200A, 200B) supported by tray 202 of stirrer 102, and the containers 200A, 200B are moved to mix the nanoparticles and the matrix fluid to provide a substantially homogeneous nanoparticle standard solution. Although two containers are shown, system 100 is not limited to two containers and can support one container or more than two containers without departing from the scope of the present disclosure. Further, although one stirrer 102 and one tray 202 are shown as supporting both containers of the nanoparticle standard, it can be understood that individual stirrers 102 and / or individual trays 202 can be used to mix the nanoparticles and the matrix fluid from individual containers to provide a substantially homogeneous nanoparticle standard solution independent of other containers. By mixing the individual containers independently, mixing of nanoparticle solutions not used for one or more future samples for analysis can be avoided, and stress associated with nanoparticle mixing can be prevented until a particular nanoparticle standard is scheduled to be used for a sample, at which point system 100 can mix that particular nanoparticle standard.

[0015] FIG. 2 shows a system 100 in a nanoparticle standard stirring state where a stirrer 102 operates to mix nanoparticle standard containers 200A and 200B. Containers 200A and 200B are fluidly coupled to a selector valve 204, and the selector valve 204 individually selects the containers and is fluidly coupled to a standard holding loop 206 via a valve 208. In an embodiment, the selector valve 204 is a valve assembly described in U.S. Patent No. 9,541,207 (incorporated herein by reference), which selects one of a plurality of ports coupled to a distribution port via a selection channel and directs fluid from the selected port to the distribution port. For example, container 200A is fluidly coupled to selector valve 204 via a fluid line 210 connected to a first port (e.g., port 204A), container 200B is fluidly coupled to selector valve 204 via a fluid line 212 connected to a second port (e.g., port 204B), and additional ports of selector valve 204 can be coupled to additional nanoparticle standard containers. The selector valve 204 fluidly couples the selected port to a distribution port (e.g., port 214) via a selection channel (e.g., channel 218 shown in FIG. 3) and can transfer the fluid received from the selected port from the distribution port to valve 208 via a fluid line 216.

[0016] Referring to FIG. 3, system 100 shows an example of a nanoparticle standard loaded state in a load configuration where container 200B is fluidly coupled to standard holding loop 206 via selector valve 204 and valve 208. In the load configuration, valve 208 fluidly connects standard holding loop 206 to vacuum loader 300 (e.g., a pump, a negative pressure source, a vacuum pump, etc.). When vacuum loader 300 operates, the nanoparticle standard from container 200B is drawn through selector valve 204 and into valve 208 via fluid line 210, selection channel 218, and fluid line 216, where the fluid is then directed to standard holding loop 206. For example, fluid line 216 can be coupled to a first port of valve 208 (e.g., port 208A), and valve 208 fluidly couples the first port to a second port (e.g., port 208B) in the load configuration, coupling fluid line 216 to standard holding loop 206. When valve 208 is in the load configuration, vacuum 300 is fluidly coupled to standard holding loop 206 via fluid line 302 coupled to a third port (e.g., port 208C), and valve 208 fluidly couples the third port to a fourth port (e.g., port 208D) to fluidly couple fluid line 302 to standard holding loop 206.

[0017] In an embodiment, vacuum loader 300 operates for a period to draw a substantially homogeneous nanoparticle standard solution from container 200B to fill the entire standard holding loop 206, and the excess standard solution is drawn back to valve 208 (e.g., towards the vacuum loader) within fluid line 302. For example, standard holding loop 206 is a fluid line (e.g., a fluid coil, etc.) having a known volume, whereby valve 208 can capture an accurate amount of nanoparticle standard within standard holding loop 206. In an embodiment, standard holding loop 206 is a holding loop with a capacity of 0.5 mL, but system 100 is not limited to a holding loop of such size and can include standard holding loops 206 with a capacity less than 0.5 mL or greater than 0.5 mL.

[0018] During the loading configuration, the stirrer 102 may be in an inactive state where no stirring or mixing of the nanoparticle standard is performed (e.g., the state shown in FIG. 3), or it may be in an active state where stirring or mixing of the nanoparticle standard is performed for some or all of the period during which the nanoparticle standard is loaded into the standard holding loop 206.

[0019] Referring to FIG. 4, the system 100 is shown with the nanoparticle standard fully loaded into the standard holding loop 206. When the standard holding loop 206 is loaded, the system 100 transitions the valve 208 from the loading configuration to the injection configuration. With the injection configuration of the valve 208, the vacuum loader 300 is disconnected from the standard holding loop 206, preventing further withdrawal of the nanoparticle standard from the container (such as containers 200A, 200B, etc.) through the standard holding loop 206. For example, the valve 206 can fluidly connect the fourth port 208D to the fifth port (e.g., port 208E) and the second port 208B to the sixth port (e.g., port 208F) to prepare for the transfer of the nanoparticle standard solution from the standard holding loop 206. In an embodiment, the valve 208 can include one or more fluid sensors that detect the fluid entering and leaving the standard holding loop 206 to determine whether the standard holding loop 206 is full. Alternatively or additionally, the system 100 includes a timer used to control the operating time of the vacuum loader 300 to provide a suitable duration for filling the standard holding loop 206.

[0020] In an embodiment, the injection configuration of valve 208 fluidly couples vacuum loader 300 and selection valve 204. For example, in the injection configuration, valve 208 fluidly couples first port 208A and third port 208C to bypass standard holding loop 206 and fluidly couple vacuum loader 300 and selection valve 204. System 100 can deactivate vacuum loader 300 when system 100 is in a state where it has loaded the nanoparticle standard, preventing further withdrawal of the nanoparticle standard from the container (such as container 200A, 200B, etc.), whereby system 100 can minimize the amount of standard used in each analysis.

[0021] Referring to FIG. 5, system 100 is shown to be in a nanoparticle standard introduction state. System 100 includes a pump 500 (e.g., a syringe pump is shown) fluidly coupled to valve 208 in the injection state, and standard holding loop 206 is fluidly coupled to pump 208 via valve 208. Pump 500 can introduce a working fluid such as water (e.g., an ultrapure water source 502 is shown) to extrude the nanoparticle standard solution held in standard holding loop 206 through valve 208 toward sample mixing portion 504 of system 100. In an embodiment, sample mixing portion 504 includes a valve 506 fluidly coupled to valve 208 to receive the nanoparticle standard extruded from standard holding loop 206. For example, valve 208 is fluidly coupled to valve 506 via a fluid line 508 coupled between sixth port 208F and port 506A of valve 506.

[0022] Valve 506 may be a selector valve for mixing two inflowing fluid streams, such as a fluid sample and a nanoparticle standard solution, as described with reference to selector valve 204. For example, valve 506 is also fluidly coupled to a sample inlet portion 510 configured to supply a fluid sample to valve 506 (this is, for example, for mixing the sample and the nanoparticle standard before sending the fluid sample to analysis system 110). For example, sample inlet portion 510 is shown with a dilution sample loop 512 configured to hold a specific amount of fluid sample, and a sample valve 514 fluidly coupled to a sample source to receive a fluid sample, such as a diluted fluid sample, from another part of system 100 (not shown). In an embodiment, the fluid sample can be supplied from an autosampler of system 100, but the present disclosure is not limited to such a configuration. Valve 506 is shown to include a mixing port 516 that receives the nanoparticle standard solution from fluid line 508 via a selection channel 518, receives a sample from sample inlet portion 510, and mixes the fluids in-line to provide a mixed sample and a standard fluid to nebulizer 520 (e.g., the nebulizer of analysis system 110). System 100 can minimize the contact time between the sample and the nanoparticle standard solution before transferring it to nebulizer 520 by mixing the sample and the nanoparticle standard solution in-line within valve 506, preventing or reducing the dissolution or damage of the nanoparticles in the standard solution by the chemicals contained in the sample before analysis by analysis system 100.

[0023] System 100 can also automatically clean the fluid flow path between the aspiration and injection of the nanoparticle standard to remove trace amounts of nanoparticle standard that may remain adhered to the fluid lines, valves, etc. For example, referring to FIG. 6, System 100 is shown in a standard cleaning state where the selection valve 204 is fluidly coupled to the actuation fluid 502, the valve 208 is in the load configuration, and the vacuum loader 300 and the standard holding loop 206 are fluidly coupled to the selection valve 204. System 100 can operate the vacuum loader 300 to aspirate a cleaning liquid (e.g., ultrapure water) through the fluid line 216, valve 208, and standard holding loop 206 coupled between the selection valve 204 and valve 208 to wash a portion of the trace nanoparticle standard. In an embodiment, the pump 500 can be filled with a cleaning liquid (e.g., from the ultrapure water source 502) in preparation for cleaning the fluid line 508 and valve 506.

[0024] Referring to FIG. 7, System 100 is shown in a purge state where a purge gas is introduced into the fluid lines and valves to remove the residual cleaning liquid. For example, the selection valve 204 is fluidly coupled to the purge gas source 700 and is shown to direct the purge gas through the fluid line 216 to the valve 208 and to push the purge gas through the standard holding loop 206 in the load configuration. The purge gas includes, but is not limited to, argon, nitrogen, an inert gas, etc., or combinations thereof. The pump 500 injects the cleaning liquid into the valve 208, the valve 208 directs the cleaning liquid into the fluid line 508, and the valve 506 flushes the trace nanoparticle standard solution from the fluid line 508. In an embodiment, System 100 can then direct the purge gas from the purge gas source into the fluid line 508 to remove the remaining rinse fluid.

[0025] An electromechanical device (e.g., an electric motor, servo, actuator, etc.) can be coupled to the components of system 100 or incorporated within system 100 to facilitate automated operation via control logic driven from outside system 100. The electromechanical device can be configured to cause the movement of the device and fluid according to various procedures such as the procedures described herein. System 100 may include a computing system having a processor or other controller configured to execute computer-readable program instructions (i.e., control logic) from a non-transitory carrier medium (such as storage media like flash drives, hard disk drives, solid state disk drives, SD cards, optical disks, etc.), or may be controlled by a computing system. The computing system can be connected to various components of system 100 directly or via one or more network connections (such as local area networks (LAN), wireless area networks (WAN or WLAN), one or more hub connections (such as USB hubs), etc.). For example, the computing system can be communicatively coupled to agitator 102, vacuum loader 300, valves described herein, pumps described herein, other components described herein, components that direct their control, or combinations thereof. When the program instructions are executed by the processor or other controller, they can cause the computing system to control system 100 (e.g., control pumps, select valves, actuators, positioning devices, etc.) according to one or more operating modes as described herein.

[0026] It should be recognized that the various functions, control operations, processing blocks, or steps described throughout this disclosure can be executed by any combination of hardware, software, or firmware. In some embodiments, various steps or functions are performed by one or more of an electronic circuit, logic gate, multiplexer, programmable logic device, application specific integrated circuit (ASIC), controller / microcontroller, or computing system. Computing systems include, but are not limited to, personal computing systems, mobile computing devices, mainframe computing systems, workstations, image computers, parallel processors, or other devices known in the art. Generally, the term "computing system" is broadly defined to include any device having one or more processors or other controllers that execute instructions from a carrier medium.

[0027] Program instructions implementing the functions, control operations, processing blocks, or steps as disclosed in the embodiments described herein can be transmitted or stored via a carrier medium. The carrier medium is a transmission medium such as, but not limited to, a wired, cable, or wireless transmission link. The carrier medium may also include a non-transitory signal carrier medium or storage medium such as, but not limited to, read-only memory, random access memory, magnetic disk or optical disk, solid state memory device or flash memory device, magnetic tape, etc.

[0028] Conclusion The subject matter has been described in language specific to structural features and / or process operations, but the subject matter defined by the claims in the appended claims is not necessarily limited to the specific features or acts described above. Rather, the specific features and acts described above are disclosed as exemplary forms of implementing the claims set forth in the appended claims.

Claims

1. An automatic processing system for a nanoparticle standard solution for spectroscopy, comprising: a stirrer configured to mix the nanoparticle standard solution in a container to provide a mixed nanoparticle standard having a substantially uniform nanoparticle distribution; a fluid preparation system fluidly coupled to the container and configured to receive the mixed nanoparticle standard, the fluid preparation system including a valve system and one or more pumps configured to contact the mixed nanoparticle standard solution with a fluid sample stream in-line through the valve system to mix the mixed sample and the nanoparticle standard solution and provide the mixed sample and the nanoparticle standard solution to the analysis system before transferring them to the analysis system; The system.

2. The fluid preparation system further includes a nanoparticle standard loop, and the valve system has a loading configuration configured to fluidly couple the container and the nanoparticle standard loop, The system according to claim 1.

3. The one or more pumps include a vacuum loader, and the valve system fluidly couples the vacuum loader to each of the nanoparticle standard loop and the container in a loading configuration such that the vacuum loader can draw the mixed nanoparticle standard into the nanoparticle standard loop, The system according to claim 2.

4. The valve system has an injection configuration configured to fluidly couple the nanoparticle standard loop to the fluid sample stream, The system according to claim 2.

5. The valve system includes a valve having a mixing port that fluidly couples a fluid line configured to transfer the mixed nanoparticle standard from the nanoparticle standard loop to a fluid line configured to transfer the fluid sample stream, enabling in-line mixing between the mixed nanoparticle standard and the fluid sample stream and providing a mixed sample and a standard fluid stream,

6. Further including an analysis system, and the valve system is configured to direct the flow of the mixed sample and the standard fluid to the analysis system, The system according to claim 5.

7. Disconnect the nanoparticle standard loop from the container while the valve system is in the injection configuration, The system according to claim 4.

8. The one or more pumps include a pump fluidly coupled to a working fluid source, and the pump is configured to introduce the working fluid from the working fluid source into the nanoparticle standard loop and extrude the mixed nanoparticle standard from the nanoparticle standard loop while the valve system is in the injection configuration, The system according to claim 2.

9. The valve system has a purge configuration fluidly coupled to a purge gas source and configured to direct purge gas to at least a portion of the system, The system according to claim 1.

10. The stirrer is configured to selectively mix the individual nanoparticle standard solutions present in each container, The system according to claim 1.

11. A method for the automatic handling of nanoparticle standard solutions for spectroscopy, Mixing the nanoparticle standard solutions in a container via a stirrer to provide a mixed nanoparticle standard solution having a substantially homogeneous distribution of nanoparticles; and Transferring the mixed nanoparticle standard via a fluid line to a fluid preparation system having a valve system and one or more pumps; and Contacting the mixed nanoparticle standard solution with a fluid sample stream through the valve system via one or more pumps, mixing the mixed sample and the nanoparticle standard solution in-line, and providing a mixed sample and a nanoparticle standard solution before transferring them to an analysis system, comprising a method.

12. The fluid preparation system further has a nanoparticle standard loop, and the valve system has a loading configuration configured to fluidly couple the container and the nanoparticle standard loop, The method according to claim 11.

13. The one or more pumps have a vacuum loader, and the valve system fluidly couples the vacuum loader to each of the nanoparticle standard loop and the container in a loading configuration such that the vacuum loader can draw the mixed nanoparticle standard into the nanoparticle standard loop, The method according to claim 12.

14. The valve system has an injection configuration configured to fluidly couple the nanoparticle standard loop to the fluid sample stream, The method according to claim 12.

15. The valve system fluidly couples a fluid line configured to transfer the mixed nanoparticle standard from the nanoparticle standard loop to a fluid line configured to transfer the fluid sample stream, and has a valve with a mixing port that enables in-line mixing between the mixed nanoparticle standard and the fluid sample stream and provides a mixed sample and a standard fluid stream, The method according to claim 14.

16. Further comprising directing the flow of the mixed sample and the standard fluid to an analysis system, The method according to claim 15.

17. Fluidly disconnecting the nanoparticle standard loop from the container while the valve system is in the injection configuration, The method according to claim 14.

18. The one or more pumps have pumps fluidly coupled to a working fluid source, the pumps being configured to introduce working fluid from the working fluid source into the nanoparticle standard loop and to extrude the mixed nanoparticle standard from the nanoparticle standard loop with the valve system in the injection configuration. The method according to claim 12.

19. The valve system has a purge configuration fluidly coupled to a purge gas source and configured to direct purge gas to at least a portion of the system. The method according to claim 11.

20. Further comprising the step of selectively mixing the individual nanoparticle standard solutions present in each container with a stirrer. The method according to claim 11.

Images