Fluid system, method of operating a fluid system, and computer program product

Abstract

The present invention relates to a fluid system for fraction collection, comprising: a switching valve, which includes a plurality of ports, the switching valve is configured to connect the ports in different configurations, the ports including a first port and a second port; an entry pipeline directly connected to the first port; and a collection device directly connected to the second port. The fluid system is configured to be in a collection configuration, with the first port and the second port connected. The ports also include a third port and a fourth port, and the fluid system also includes a buffer section directly connected to the third port and the fourth port. The fluid system also includes a first collection reservoir and is configured to position the collection device to discharge the fluid into the first collection reservoir. The fluid system is also configured to be in a buffer configuration, which causes the fluid to flow through the entry pipeline, the first port, the third port, the buffer section, the fourth port, the second port and the collection device in the buffer configuration. The present invention also relates to a method for operating a fluid system and a computer program product.

Description

Technical Field

[0001] The present invention relates to a fluid system and method for fraction collection, which can be used at least as a part in a liquid chromatography system, preferably a high performance liquid chromatography (HPLC) system. More particularly, it relates to a flushing function and a switching valve configured for use in a fluid system for fraction collection. Background Art

[0002] Chromatographic systems are widely used to separate a sample into its various components. More specifically, chromatography is a group of analytical methods used to take a sample (e.g., for a complex mixture) and separate its component substances, or analytes, from one another. In general, analytical chromatography is used to determine the presence and sometimes the concentration of an analyte in a sample.

[0003] Some components (which may be referred to as fractions) separated from the sample may require further sample processing, such as separation and analysis. They can then be collected in a target vessel as separated fractions. An embodiment of the present invention relates to a fraction collector, which is a fluid system, preferably a device of an HPLC system, for collecting those target fractions. It is understandable that, in the case of not collecting fractions, chromatography may only produce information about the composition of the sample, but may not help to separate different components. Therefore, fraction collection can form a part of most chromatographic separation processes. For example, when purifying a sample or when chemical tests are performed on different components of a sample, the separation of each component may be of concern, which may be particularly advantageous for medical applications.

[0004] In a liquid chromatography system, the sample to be analyzed is pushed through a separation column by an analytical pump with the help of a solvent (which may be called a mobile phase). The separation column may be filled with an adsorbent material (which may be called a stationary phase), which may interact with the component molecules of the sample. Depending on the strength of the interaction of the different components present in the sample with the stationary phase, they are eluted from the separation column at different times. They can then be detected as peaks at different times by a detector downstream of the separation column, wherein components with strong interactions are eluted as peaks later in time than components with weak interactions.

[0005] As mentioned above, it may be advantageous to collect the fractions washed out from the separation column downstream of the detector for further analysis. For example, the sample may include multiple components, which all weakly interact with the first stationary phase in the separation column. So, the mixture of these components can be washed out relatively early in the separation process. So, it may be advantageous to repeat the separation process with different stationary phases to allow further analysis of this mixture that only weakly interacts with the first stationary phase. In the case where only a limited volume of sample can be used for analysis, this may be particularly advantageous, so that fractions can be collected from the first separation to save sample volume.

[0006] The collection of fractions can be based on detector signals, for example, based on the identification of certain peaks, or based on the residence time in the separation column, for example, the collection of fractions washed out from the separation column between a certain start time and an end time. These can be classified as peak-based and time-based fractionation, respectively. When the fractions to be collected have a known and stable residence time or a known and stable peak shape, time-based fractionation can be advantageously used so that the start and end of the fraction collection process can be, for example, based on the slope of the peak shape. This may also be particularly advantageous for complex samples, in which it may be difficult to accurately distinguish between individual peaks, so that peak-based methods may produce inaccurate collections. However, time-based fractionation can provide low resolution because all components that may be washed out in the time window selected for collection will be collected in the fractions.

[0007] On the other hand, peak-based fractionation may be advantageous when the dwell time and / or peak shape are unknown or unstable. However, it may provide higher resolution than time-based fractionation because only known peaks are collected as fractions.

[0008] A relevant consideration for a fraction collection system (which may be referred to as a fraction collector) may be, for example, to minimize the volume of fluid lost when switching reservoirs to collect more than one fraction. Another consideration may be the purity of the collected fractions, for example for fractions that may be closely spaced during a separation.

[0009] An example of mixing might be carryover (carryover) due to, for example, not completely emptying the collection needle at the end of collecting the previous fraction. Summary of the invention

[0010] In view of the above, it is generally desirable to have a technique that allows sample fractionation. In other words, it is generally desirable to have a technique that allows samples to be eluted at different times to be collected separately from each other. These are the objects of the present invention. More specifically, it is an object of the present invention to provide a fraction collection technique with high recovery and little or no carryover, especially for closely spaced fractions / peaks and very small volumes.

[0011] The present invention meets at least some of these objectives.

[0012] In a first aspect, the present invention relates to a fluid system, wherein the fluid system comprises: a switching valve, the switching valve comprises a plurality of ports, wherein the switching valve is configured to connect the ports in different configurations, wherein the ports comprise a first port and a second port; an inlet line, the inlet line is directly connected to the first port; a collecting device, the collecting device is directly connected to the second port; and wherein the fluid system is configured to be in a collecting configuration, in which the first port and the second port are connected. This configuration may represent a typical configuration of a fluid system for fraction collection. The eluate from the analytical device upstream of the inlet line may flow into the collecting device and then be collected in the collecting reservoir. The delay volume (amount) between the eluate from the analytical detector and the fraction appearing at the collecting device may allow time to align the collecting device with the collecting reservoir, which may be advantageous. In general, in this specification, when a unit is said to be directly connected to a port of a switching valve (e.g., as if the inlet line is directly connected to the first port), this means that there is a connection between the unit and the port, and there is no other port of the switching valve in the connection.

[0013] The port may include a third port and a fourth port, and the fluid system may include a buffer section directly connected to the third port and the fourth port. A fluid system having these components can be used to perform multi-fraction collection with a high recovery rate. In a typical fraction collection system, when switching from the collection of one fraction to the collection of the next fraction, an intermediate step can be used to allow the fluid to flow out into the waste material to ensure that the fractions are not mixed. However, as will be described below, the buffer section can help collect different fractions, for example, less volume is discharged into the waste material. In other words, the buffer section can prevent undesirable fractions / peaks from flowing into the collection device. Mixed fractions or peaks may only exist in the buffer section. Different fractions / peaks, even closely arranged fractions / peaks can be isolated, while using the buffer section to reduce carryover.

[0014] The fluid system may be configured in a buffer configuration in which the first port and the third port are connected and the fourth port and the second port are connected.

[0015] The ports may include a pump port directly connected to a pump and a waste port directly connected to a waste. A pump (which may be a piston pump) connected to one port of the switching valve may be advantageous for cleaning the buffer segment between collecting different fractions. It may first be filled with a clean mobile phase (if the fluid system includes an HPLC system) or an additional cleaning / cleaning solvent. Then, it can be used to clean the buffer segment of the fluid connected to the switching valve. Cleaning the buffer segment ensures that the buffer segment is filled with a clean solvent or a clean mobile phase.

[0016] The above-mentioned fluid system can be configured to be a buffer cleaning configuration, wherein the pump port is connected to the fourth port, and the third port is connected to the waste port. This allows the buffer section to be rinsed. As mentioned above, the mixed fraction / peak can only exist in the buffer section in some embodiments. After the flushing is completed, the mixed fraction / peak will be cleaned and washed into the waste, for example, by the piston of the actuating pump. Then, for example, the buffer section can be refilled with a clean mobile phase or a clean solvent that has been stored in the cavity of the (piston) pump.

[0017] These ports may include a drain port that connects directly to waste.

[0018] The above fluid system may also be configured in a discharge configuration in which the first port is connected to the discharge port.

[0019] The above fluid system can be configured so that the buffer cleaning configuration and the discharge configuration are the same. Connecting the discharge port and the waste port directly to the waste can have the following advantages: for example, when a buffer section is used between the collection of two fractions, it allows the buffer section to be cleaned and / or refilled while the fluid system is ready to collect the next fraction. For example, when the collection device moves between the collection reservoirs, the flow through the inlet pipeline can be introduced into the waste through the discharge port. At the same time, the buffer section can also distribute its contents into the waste. This may help to improve the efficiency of the fraction collection process.

[0020] The fluid system may also include a solvent reservoir configured to be connected to a port of a switching valve and allowing solvent to be drawn therefrom. If the fluid system is an HPLC system, the solvent may be the mobile phase used in the HPLC system. Therefore, the mobile phase may additionally serve as a flushing solvent for flushing out or distributing the remaining liquid in a collecting device, which may include a collecting tube and a collecting needle, rather than providing additional cleaning solvents separately for this purpose. This may help reduce the complexity of the fluid system, simplify operation, and result in less waste.

[0021] These ports may include a solvent port that connects directly to a solvent reservoir.

[0022] The above fluid system can also be configured in a pump-loaded configuration, wherein the solvent port is connected to the pump port. This allows the pump to easily draw solvent from the solvent reservoir.

[0023] The pump loading configuration may be the same as the collection configuration. As described above, in the buffer segment cleaning configuration, the buffer segment may be cleaned and / or refilled with solvent that has been stored in the chamber of the (piston) pump. An advantage of the pump loading configuration and the collection configuration may be that after refilling the buffer segment with clean solvent, the pump may be refilled with clean solvent while collecting fractions. This may help to increase the efficiency of the collection process.

[0024] The switching valve may comprise a first connection piece for connecting the ports. It may be advantageous for the connection piece to have a dead volume very close to zero between the two ports it connects.

[0025] The first connector may connect the first port and the second port in a collection configuration, connect the first port and the exhaust port in a exhaust configuration, and connect the first port and the third port in a buffer configuration.

[0026] The switching valve may include a second connector for connecting the ports. The second connector may connect the solvent port and the pump port in the collection configuration, connect the fourth port and the pump port in the discharge configuration, and connect the second port and the fourth port in the buffer configuration.

[0027] The switching valve may include a third connector for connecting the ports. The third connector may connect the third port and the discharge port in the collection configuration, connect the third port and the waste port in the discharge configuration, and connect the waste port to the dead end in the buffer configuration.

[0028] The fluid system may also include a purge section configured to receive the collection device. This may help clean the collection device between collection of different fractions, resulting in less carryover.

[0029] The fluid system may further comprise a first collection reservoir, wherein the fluid system may be configured to position the collection device to discharge the fluid into the first collection reservoir.

[0030] The fluid system may include a second collection reservoir, wherein the fluid system may be configured to position the collection device to discharge fluid into the second collection reservoir.

[0031] The collection device may include a collection needle. The collection needle may be selected based on the sample to be collected. A relevant consideration may be the viscosity or surface tension of the sample, as a higher surface tension will mean a greater tendency to adhere to the surface of the collection needle.

[0032] The collecting means may comprise a collecting tube.

[0033] The fluid system may also include a flow sensor configured to measure a flow rate of the fluid flowing therethrough.

[0034] The above fluid system can be configured such that the flow sensor is configured to measure the flow rate of the fluid discharged into the waste. The measurement of the flow rate can be used to determine the time taken for the eluate to flow from the analytical detector to the collection device. The flow time may be related to determining the speed at which the collection needle can be positioned on the collection reservoir, or to determining the speed at which the switching valve can be switched between different configurations as part of the fraction collection process.

[0035] The fluid system may further include a control unit configured to switch between different configurations of the fluid system.

[0036] The control unit may be configured to switch the configuration of the switching valve to switch the configuration of the fluid system.

[0037] Switching the configuration of the switching valve may be based on measuring the flow rate of the fluid discharged into the waste. The control unit may be a microprocessor and may use, for example, measurements from a flow sensor to determine when to switch the configuration of the switching valve. For example, once the first fraction is collected and a second fraction to be collected is detected upstream of the entry line, the control unit may switch the switching valve from the collection configuration to the buffer section configuration, so that the fluid flow is directed through the buffer section. This allows the first fraction to fill the buffer section with a clean solvent and may result in less sample loss.

[0038] The control unit may also be configured to position the collection device to discharge the fluid into the collection reservoir. For example, once the first fraction has been collected and the second fraction is to be further collected, the control unit may move the collection device to the correct position above the collection reservoir for the second fraction. It may be particularly advantageous to use a control unit for this process to ensure that the timing (choice of time) between the collection of different fractions is accurately controlled and reproducible.

[0039] The pump may be a metering device. It may include a piston and a housing. Alternatively, it may be a flushing pump. It may also include a container containing a pressurized gas.

[0040] The fluid system may further comprise an analytical detector located upstream of the first port. For example, the analytical detector may be used to indicate the arrival of different fractions to the control unit so as to bring the switching valves and the collecting device into the appropriate configuration for collecting the fractions in their corresponding collecting reservoirs.

[0041] The above-mentioned fluid system may be a liquid chromatography system, preferably a high performance liquid chromatography system.

[0042] The above solvents may be the same as the mobile phase used in the liquid chromatography system. This may be different from a typical fraction collection process, which may require special solvents to be provided to clean the collection tubes and collection device, and thus may require more operations and / or special solvents. Alternatively, no cleaning solvents are used to clean the collection device, which may result in more carryover.

[0043] The above solvents may be different from the mobile phase used in the liquid chromatography system. However, this may not be a preferred embodiment because the use of additional solvents will increase the complexity of the operation and the system.

[0044] The above-mentioned solvent can be any one of an organic solvent, an inorganic solvent, a polar solvent or a non-polar solvent.

[0045] Switching the switching valve from the discharge configuration to the collection configuration may include rotating the switching valve by an angle between 10° and 80°, preferably between 20° and 70°, and more preferably between 30° and 60°. Smaller angles may facilitate rapid switching of the switching valve. However, they may also make the arrangement of the ports on the switching valve more complicated.

[0046] Switching the switching valve from the collecting configuration to the buffering configuration may include rotating the switching valve by an angle between 10° and 80°, preferably by an angle between 20° and 70°, and more preferably by an angle between 30° and 60°.

[0047] The switching valve may include ports such that the second port is between the fourth port and the exhaust port, the third port is between the exhaust port and the waste port, and the solvent port is between the waste port and the pump port.

[0048] The switching valve may include ports such that the fourth port is between the second port and the pump port, the discharge port is between the second port and the third port, the waste port is between the third port and the solvent port, and the pump port is between the solvent port and the fourth port.

[0049] The switching valve may include ports such that the first port is located at substantially the same distance from the other ports.

[0050] The cleaning section can also be configured to draw solvent from the solvent reservoir for cleaning the outer surface of the collecting needle. This can help simplify the system because the same solvent used to clean the buffer section can be used to clean the outer surface of the collecting needle.

[0051] The above-mentioned collecting device can be configured to be positioned in one dimension. For example, this may be the case when a plurality of collecting reservoirs are placed adjacent to each other in a one-dimensional array. This may allow the collecting device to be moved over the collecting reservoirs with a simpler control program. However, this may also limit the number of collecting reservoirs that can be filled with fractions.

[0052] Alternatively, the collecting device may be configured for two-dimensional positioning. This may allow a larger number of collecting reservoirs to be filled with fractions by only a small movement of the collecting device. However, as will be appreciated, this may involve a more complex alignment procedure of the collecting device on the collecting reservoir.

[0053] According to a second aspect, the present invention also relates to a switching valve. The switching valve comprises a plurality of ports, and the switching valve is configured to connect the ports in different configurations. The ports comprise a first port, a second port and a discharge port, the switching valve comprises a stator, the stator comprises a plurality of ports, and the switching valve comprises a rotor, wherein the rotor comprises at least one connector for connecting the ports in different configurations. When the term discharge port is used with the switching valve, it should be understood that this is only for consistency with the terminology used when describing the system. That is, the term discharge port only stipulates that the corresponding port can also be used as a discharge port in principle, but this does not require that the port is actually used as such a discharge port. When used to describe the valve, corresponding considerations also apply to the terms collection configuration, discharge configuration and buffer configuration. Similarly, these terms are mainly used to distinguish between different configurations, and the corresponding configurations do not necessarily have to be actually used for collection, discharge and buffer functions.

[0054] The at least one connecting element may be at least one groove.

[0055] One of the at least one (connecting) piece may comprise an L-shaped groove comprising a radial section and a circumferential section.

[0056] At least one of the (connecting) members comprises 3 connecting members, and each of the 2 other connecting members may be located on opposite sides of the L-shaped slot.

[0057] The rotor may include a slot connected to the second port and extending between the second port and the exhaust port.

[0058] The rotor may include a third port.

[0059] The rotor may include a slot connected to the discharge port and extending between the discharge port and the third port.

[0060] A subset of the plurality of ports may be located on a circle around the first port.

[0061] The switching valve may be configured in a collecting configuration to fluidly connect the first port and the second port.

[0062] The switching valve may be configured in a discharge configuration to fluidly connect the first port and the discharge port.

[0063] The switching valve may be configured to transition from a collecting configuration to a drain configuration such that the first port is always connected to the second port or the drain port during the transition.

[0064] The switching valve may be configured in a buffer configuration, wherein the first port and the third port are connected.

[0065] The switching valve may be configured to transition from the exhaust configuration to the buffer configuration such that the first port is always connected to the exhaust port or the third port during the transition.

[0066] In the collection configuration, the fluid connection between the first port and the second port may be free of dead volume.

[0067] In the exhaust configuration, the fluid connection between the first port and the exhaust port may be free of dead volume.

[0068] In the buffered configuration, the fluid connection between the first port and the third port may not include a dead volume.

[0069] In the described system, the switching valve may be implemented according to the switching valve of the second aspect.

[0070] According to a third aspect, the present invention relates to a method for operating the above-mentioned fluid system, wherein the method comprises: placing the fluid system in a collecting configuration, and allowing the fluid flow to enter a first collecting reservoir through an entry line, a first port, a second port and a collecting device in the collecting configuration.

[0071] The method may include placing the fluid system in a buffer configuration and flowing a second fluid stream through an entry line, a first port, a third port, a buffer section, a fourth port, a second port, and a collection device in the buffer configuration.

[0072] The second fluid flow can cause fluid to flow into the first collection reservoir. Thus, the buffer section can be used to direct the fluid flow near the end of the collection of one fraction and before the start of the collection of the next fraction. This can help collect two fractions, even if they are closely arranged, without contaminating each other. The contaminated fraction is only present in the buffer section and can be cleaned under the subsequent buffer section cleaning configuration.

[0073] The method may further include: after the fluid system is in the buffer configuration, making the fluid system in the buffer section cleaning configuration, and the fluid system makes the cleaning flow flow through the pump port, the fourth port, the buffer section, the third port, the waste port and flow to the waste in the buffer section cleaning configuration.

[0074] The method may further include: after the fluid system is in the buffer section cleaning configuration, placing the fluid system in the collection configuration again, and the fluid system allows the fluid flow to enter the second collection reservoir through the entry pipeline, the first port, the second port and the collection device in the collection configuration.

[0075] The method may further include measuring a dead volume of a flow path of the fluid in any configuration of the fluid system.

[0076] The method may also include determining when to switch the fluid system configuration using the dead volume measured in a certain configuration and the fluid flow rate measured by the flow sensor.

[0077] The method may further include switching the configuration of the fluid system using the control unit.

[0078] The method may further include switching the position of the collection device to switch the configuration of the fluid system.

[0079] The method may further include: switching the configuration of the switching valve to switch the configuration of the fluid system. For example, the switching valve may switch between a collection configuration, a buffer section configuration, and a buffer section cleaning configuration, wherein in each of these configurations, a plurality of connectors connect different port pairs.

[0080] The method may also include: after the fluid system is in the collection configuration, placing the fluid system in a discharge configuration, and the fluid system causes a purge flow through the entry line, the first port and to the waste in the discharge configuration. This may be a configuration in which the fluid system is used to collect fractions without an intermediate buffer section purge configuration. Omitting the buffer section purge configuration may help further improve the efficiency of the collection process.

[0081] The method may further include: after the fluid system is in the discharge configuration, placing the fluid system in the collection configuration again, and the fluid system allows the fluid flow to flow into the second collection reservoir through the entry pipeline, the first port, the second port and the collection device in the collection configuration.

[0082] When the fluid flows into the first collection reservoir, the first sample component may be collected in the first collection reservoir, and when the fluid flows into the second collection reservoir, the second sample component may be collected in the second sample reservoir.

[0083] According to a third aspect, the present invention relates to a computer program product comprising instructions, which are configured to, when run on a control unit of a fluid system, cause the fluid system to perform a method according to any of the foregoing method embodiments. For example, such a product may include instructions that, once a fraction appears at an analytical detector, switches a switching valve to, for example, a collection configuration. Alternatively, if a first fraction is being collected and a second fraction appears at the analytical detector, the control unit may be programmed to switch the switching valve to a buffer segment configuration. Similarly, at the end of collecting the first fraction, the control unit may be programmed to position the collection device above the second collection reservoir.

[0084] In general, embodiments of the present technology may therefore involve a fluidics design that makes it possible to collect closely spaced fractions / peaks with a flushing function (flushing out or distributing the remaining liquid in the collection tube and needle to improve recovery and reduce carryover). In embodiments, a valve that may be referred to as a fraction valve (implemented as a multi-port rotary valve) may be used for a fraction collector that is embedded inside the product and directs HPLC system flow to a waste, collection vessel, or flush position (still connected to the collection vessel) by high-speed switching in at least three positions, namely a waste position, a collection position, and a flush position.

[0085] Next, embodiments of the system will be discussed. These embodiments are abbreviated with the letter "S" followed by a number. All embodiments of the system mentioned in this article refer to these embodiments.

[0086] S1. A fluid system, wherein the fluid system comprises:

[0087] a switching valve, the switching valve comprising a plurality of ports, wherein the switching valve is configured to connect the ports in different configurations, wherein the ports comprise a first port and a second port;

[0088] an inlet line, the inlet line being directly connected to the first port;

[0089] a collection device directly connected to the second port; and

[0090] Therein, the fluid system is configured in a collecting configuration, wherein the first port and the second port are connected.

[0091] S2. The fluid system according to the previous embodiment,

[0092] Wherein, the ports include a third port and a fourth port;

[0093] The fluid system includes a buffer section, which is directly connected to the third port and the fourth port.

[0094] S3. The fluid system according to the previous embodiment,

[0095] The fluid system is configured to be in a buffer configuration, wherein the first port is connected to the third port, and the fourth port is connected to the second port.

[0096] S4. A fluid system according to any one of the preceding embodiments,

[0097] Among them, the ports include a pump port directly connected to the pump and a waste port directly connected to the waste.

[0098] S5. A fluid system according to the preceding embodiment and having the features of embodiment S2,

[0099] The fluid system is configured to be in a buffer zone cleaning configuration, wherein the pump port is connected to the fourth port, and the third port is connected to the waste port.

[0100] S6. A fluid system according to any one of the preceding embodiments,

[0101] Among other things, these ports include a drain port that connects directly to waste.

[0102] S7. The fluid system according to the previous embodiment,

[0103] Therein, the fluid system is configured in a discharge configuration, wherein the first port is connected to the discharge port.

[0104] S8. A fluid system according to the preceding embodiment and having the features of embodiment S5, wherein the buffer wash configuration and the drain configuration are the same.

[0105] S9. A fluid system according to any of the preceding embodiments, wherein the fluid system further comprises a solvent reservoir configured to be connected to (one) port of the switching valve and to allow solvent to be drawn therefrom.

[0106] S10. The fluid system according to the previous embodiment,

[0107] Among other things, these ports include a solvent port that is directly connected to a solvent reservoir.

[0108] S11. A fluid system according to the previous embodiment and having the features of embodiment S4,

[0109] Therein, the fluid system is configured in a pump-loaded configuration, wherein the solvent port and the pump port are connected.

[0110] S12. The fluid system of the preceding embodiment, wherein the pump loading configuration is the same as the collection configuration.

[0111] S13. A fluid system according to any of the preceding embodiments, wherein the switching valve comprises a first connector for connecting the port.

[0112] S14. The fluid system according to the preceding embodiment, wherein the first connector connects the first port and the second port in a collecting configuration.

[0113] S15. The fluid system according to any one of the preceding two embodiments, wherein the first connector connects the first port and the exhaust port in an exhaust configuration.

[0114] S16. A fluid system according to any of the preceding embodiments and with features of embodiments S3 and S13, wherein the first connector connects the first port and the third port in a buffer configuration.

[0115] S17. A fluid system according to any of the preceding embodiments, wherein the switching valve comprises a second connector for connecting the port.

[0116] S18. A fluid system according to the preceding embodiment and with features of embodiments S4 and S10, wherein the second connector connects the solvent port and the pump port in the collection configuration.

[0117] S19. A fluid system according to any one of the two preceding embodiments and with features of embodiments S2 and S4, wherein the second connector connects the fourth port and the pump port in a discharge configuration.

[0118] S20. A fluid system according to any of the preceding embodiments and with features of embodiments S2 and S17, wherein the second connector connects the second port and the fourth port in a buffer configuration.

[0119] S21. A fluid system according to any of the preceding embodiments, wherein the switching valve comprises a third connector for connecting the port.

[0120] S22. The fluid system according to the previous embodiment, wherein the third connector connects the third port and the exhaust port in the collection configuration.

[0121] S23. A fluid system according to the second to last embodiment and with features of embodiments S3 and S7, wherein a third connector connects the third port and the waste port in a drain configuration.

[0122] S24. A fluid system according to any of the preceding embodiments and with features of embodiments S3, S4 and S21, wherein a third connector connects the waste port to a dead end in a buffer configuration.

[0123] S25. A fluid system according to any of the preceding embodiments, wherein the fluid system comprises a cleaning section configured to receive a collection device.

[0124] S26. A fluid system according to any of the preceding embodiments, wherein the fluid system comprises a first collection reservoir, and wherein the fluid system is configured to position the collection device to discharge the fluid into the first collection reservoir.

[0125] S27. A fluid system according to any of the preceding embodiments, wherein the fluid system comprises a second collection reservoir, and wherein the fluid system is configured to position the collection device to discharge the fluid into the second collection reservoir.

[0126] S28. A fluid system according to any of the preceding embodiments, wherein the collecting device comprises a collecting needle.

[0127] S29. A fluid system according to any of the preceding embodiments, wherein the collecting device comprises a collecting tube.

[0128] S30. A fluid system according to any one of the preceding embodiments, wherein the fluid system further comprises a flow sensor configured to measure a flow rate of a fluid flowing through it.

[0129] S31. A fluid system according to the preceding embodiment and with the features of embodiment S4, wherein the flow sensor is configured to measure the flow rate of the fluid being discharged into the waste.

[0130] S32. A fluid system according to any of the preceding embodiments, wherein the fluid system further comprises a control unit configured to switch between different configurations of the fluid system.

[0131] S33. The fluid system according to the previous embodiment, wherein the control unit is configured to switch the configuration of the switching valve to switch the configuration of the fluid system.

[0132] S34. A fluid system according to any of the preceding embodiments and with the features of embodiments S31 and S32, wherein the configuration of the switching switching valve is based on a measurement of the flow rate of the fluid being (discharged) into the waste.

[0133] S35. A fluid system according to any of the preceding embodiments and with features of embodiment S32 and features of any of embodiments S26 and S27, wherein the control unit is further configured to position the collection device to discharge the fluid into the collection reservoir.

[0134] S36. A fluid system according to any of the preceding embodiments and having the features of embodiment S4, wherein the pump is a metering device.

[0135] S37. A fluid system according to any of the preceding embodiments and having the features of embodiment S4, wherein the pump comprises a piston and a housing.

[0136] S38. A fluid system according to any of the preceding embodiments and having the features of embodiment S4, wherein the pump is a flushing pump.

[0137] S39. A fluid system according to any of the preceding embodiments and having the features of embodiment S4, wherein the pump comprises a container containing pressurized gas.

[0138] S40. A fluid system according to any one of the preceding embodiments, wherein the fluid system further comprises an analytical detector located upstream of the first port.

[0139] S41. A fluid system according to any of the preceding embodiments, wherein the fluid system is a liquid chromatography system, preferably a high performance liquid chromatography system.

[0140] S42. A fluid system according to the preceding embodiment and having the features of embodiment S9, wherein the solvent is the same as the mobile phase used in the liquid chromatography system.

[0141] S43. A fluid system according to the second-to-last embodiment and having the features of embodiment S9, wherein the solvent is different from the mobile phase used in the liquid chromatography system.

[0142] S44. A fluid system according to any of the preceding embodiments and having the features of embodiment S9, wherein the solvent is an organic solvent.

[0143] S45. A fluid system according to any of the preceding embodiments and having the features of embodiment S9, wherein the solvent is an inorganic solvent.

[0144] S46. A fluid system according to any of the preceding embodiments and having the features of embodiment S9, wherein the solvent is a polar solvent.

[0145] S47. A fluid system according to any of the preceding embodiments and having the features of embodiment S9, wherein the solvent is a non-polar solvent.

[0146] S48. According to the fluid system described in any of the aforementioned embodiments and with the characteristics of embodiment S7, switching the switching valve from the discharge configuration to the collection configuration includes: rotating the switching valve to an angle between 10° and 80°, preferably an angle between 20° and 70°, and more preferably an angle between 30° and 60°.

[0147] S49. According to the fluid system described in any of the aforementioned embodiments and with the characteristics of embodiment S3, switching the switching valve from the collection configuration to the buffer configuration includes: rotating the switching valve to an angle between 10° and 80°, preferably an angle between 20° and 70°, and more preferably an angle between 30° and 60°.

[0148] S50. A fluid system according to any of the preceding embodiments and having the features of embodiments S2, S4, S6 and S10, wherein:

[0149] The second port is between the fourth port and the exhaust port;

[0150] a third port between the drain port and the waste port; and

[0151] The solvent port is between the waste port and the pump port.

[0152] S51. A fluid system according to any of the preceding embodiments and having the features of embodiments S2, S4, S6 and S10, wherein:

[0153] The fourth port is between the second port and the pump port;

[0154] The exhaust port is between the second port and the third port;

[0155] The waste port is between the third port and the solvent port; and

[0156] The pump port is between the solvent port and the fourth port.

[0157] S52. A fluid system according to any one of the preceding two embodiments, wherein the distances between the first port and the other ports are substantially the same.

[0158] S53. A fluid system according to any of the preceding embodiments and with features of embodiments S9, S25 and S28, wherein the cleaning section is further configured to draw solvent from a solvent reservoir for cleaning the outer surface of the collection needle.

[0159] S54. A fluid system according to any of the preceding embodiments, wherein the collection device is configured for one-dimensional positioning.

[0160] S55. A fluid system according to any of the preceding embodiments but without the features of the previous embodiment, wherein the collection device is configured for two-dimensional positioning.

[0161] Next, embodiments of the valve will be discussed. These embodiments are abbreviated with the letter V followed by a number. All references to embodiments of the valve in this document refer to these embodiments.

[0162] V1. A switching valve, wherein the switching valve comprises a plurality of ports, wherein the switching valve is configured to connect the ports in different configurations, wherein the ports comprise a first port (0), a second port (2), and a drain port (3);

[0163] Wherein, the switching valve includes a stator, wherein the stator includes a plurality of ports;

[0164] Therein, the switching valve comprises a rotor, wherein the rotor comprises at least one connection piece for connecting the ports in different configurations.

[0165] V2. The switching valve according to the preceding embodiment, wherein at least one connecting member is at least one groove.

[0166] V3. A switching valve according to any of the preceding valve embodiments, wherein one of the at least one (connecting) parts comprises an L-shaped groove comprising a radial section and a circumferential section.

[0167] V4. A switching valve according to the previous embodiment, wherein at least one (connection) member comprises 3 connections, and each of the 2 other connections is located on opposite sides of the L-shaped groove.

[0168] V5. A switching valve according to any of the preceding valve embodiments, wherein the rotor comprises a slot connected to the second port and extending between the second port and the exhaust port.

[0169] V6. A switching valve according to any of the preceding valve embodiments, wherein the rotor comprises a third port.

[0170] V7. A switching valve according to the preceding embodiment and with the features of embodiment V5, wherein the rotor comprises a slot connected to the discharge port and extending between the discharge port and the third port.

[0171] V8. A switching valve according to any of the preceding valve embodiments, wherein a subset of the plurality of ports are located on a circle around the first port.

[0172] V9. A switching valve according to any one of the aforementioned valve embodiments, wherein the switching valve is configured to be in a collecting configuration to fluidly connect the first port and the second port.

[0173] V10. The switching valve according to any of the preceding valve embodiments, wherein the switching valve is configured in a drain configuration to fluidly connect the first port and the drain port.

[0174] V11. A switching valve according to the preceding embodiment and with the features of the aforementioned second embodiment, wherein the switching valve is configured to transition from a collecting configuration to a drain configuration such that the first port is always connected to the second port or the drain port during the transition.

[0175] V12. A switching valve according to any of the preceding embodiments and with the features of embodiment V6, wherein the switching valve is configured in a buffer configuration, wherein the first port and the third port are connected.

[0176] V13. The switching valve according to the preceding embodiment and with the features of embodiment V10, wherein the switching valve is configured to transition from the exhaust configuration to the buffer configuration such that the first port is always connected to the exhaust port or the third port during the transition.

[0177] V14. A switching valve according to any of the preceding embodiments and with the features of embodiment V9, wherein in the collection configuration, the fluid connection between the first port and the second port is free of dead volume.

[0178] V15. A switching valve according to any of the preceding embodiments and with the features of embodiment V10, wherein in the exhaust configuration the fluid connection between the first port and the exhaust port is free of dead volume.

[0179] V16. A switching valve according to any of the preceding embodiments and with the features of embodiment V12, wherein, in the buffer configuration, the fluid connection between the first port and the third port is free of dead volume.

[0180] S56. A system according to any one of the embodiments of the aforementioned system, wherein the switching valve is implemented according to any one of the embodiments of the aforementioned valve.

[0181] Below, the embodiments of the method will be discussed. These embodiments are abbreviated with the letter "M" followed by a number. All embodiments of the method mentioned in this article refer to these embodiments.

[0182] M1. A method of operating a fluid system according to any of the preceding embodiments and with the features of embodiment S26, wherein the method comprises:

[0183] The fluid system is placed in a collecting configuration, and the fluid flow is caused to flow into the first collecting reservoir through the inlet line, the first port, the second port and the collecting device in the collecting configuration.

[0184] M2. The method of the preceding embodiment, wherein the fluid system includes the features of embodiment S3,

[0185] Among them, the method includes:

[0186] The fluid system is placed in a buffer configuration, and a second fluid stream is caused to flow through the inlet line, the first port, the third port, the buffer section, the fourth port, the second port, and the collection device in the buffer configuration.

[0187] M3. According to the method described in the previous embodiment,

[0188] Therein, the second fluid flow causes the fluid to flow into the first collection reservoir.

[0189] M4. The method according to the above two embodiments, wherein the fluid system includes the features of embodiment S5,

[0190] The method further comprises:

[0191] After the fluid system is in the buffer configuration, the fluid system is in the buffer section cleaning configuration, and the fluid system allows the cleaning flow to flow through the pump port, the fourth port, the buffer section, the third port, the waste port and to the waste in the buffer section cleaning configuration.

[0192] M5. The method of the preceding embodiment, wherein the fluid system includes the features of embodiment S27,

[0193] The method further comprises:

[0194] After the fluid system is in the buffer stage cleaning configuration, the fluid system is again in the collection configuration, and the fluid system allows the fluid flow to flow into the second collection reservoir through the inlet pipeline, the first port, the second port and the collection device in the collection configuration.

[0195] M6. A method according to any one of the embodiments of the aforementioned method, wherein the method further comprises: measuring the dead volume of the flow path of the fluid under any configuration of the fluid system.

[0196] M7. A method according to the previous embodiment, wherein the fluid system includes the features of embodiment S30, wherein the method further comprises: using the dead volume measured under a certain configuration and the fluid flow rate measured by the flow sensor to determine the time to switch the fluid system configuration.

[0197] M8. A method according to any one of the embodiments of the aforementioned method, wherein the fluid system includes the features of embodiment S32, wherein the method further comprises: using a control unit to switch the configuration of the fluid system.

[0198] M9. A method according to any one of the embodiments of the aforementioned method, wherein the fluid system includes the features of embodiment S35, wherein the method further comprises: switching the position of the collection device to switch the configuration of the fluid system.

[0199] M10. A method according to any one of the embodiments of the aforementioned method, wherein the fluid system includes the features of embodiment S33, wherein the method further comprises: switching the configuration of the switching valve to switch the configuration of the fluid system.

[0200] M11. The method according to any one of the embodiments of the preceding method, wherein the fluid system comprises the features of embodiment S7,

[0201] The method further comprises:

[0202] After the fluid system is in the collection configuration, the fluid system is in the discharge configuration ( Fig. 9 ), and the fluid system allows the purge flow to flow through the pipeline, the first port and to the waste in a discharge configuration.

[0203] M12. A method according to the previous embodiment, characterized in that the fluid system includes the features of embodiment S27,

[0204] The method further comprises:

[0205] After the fluid system is in the discharge configuration, the fluid system is again in the collection configuration, and the fluid system flows the fluid through the inlet line, the first port, the second port and the collection device in the collection configuration and into the second collection reservoir.

[0206] M13. A method according to any one of the embodiments of the aforementioned method and with the characteristics of embodiments M5 and / or M12, wherein when the fluid flows into the first collection reservoir, the first sample component is collected in the first collection reservoir, and when the fluid flows into the second collection reservoir, the second sample component is collected in the second sample reservoir.

[0207] P1. A computer program product comprising instructions, which are configured to cause the fluid system to perform a method according to any one of the embodiments of the preceding method when the instructions are run on a control unit of the fluid system. BRIEF DESCRIPTION OF THE DRAWINGS

[0208] Figure 1 The fluid system is shown in an idle state;

[0209] Figure 2a -2d shows a switching valve configured for use in a fluid system;

[0210] Figure 3 shows the fluid system in a drain configuration, wherein the washout is directed to a waste reservoir;

[0211] Figure 4 shows the fluid system in a collection configuration, wherein the eluate is collected in a collection reservoir;

[0212] Figure 5 shows a fluid system in a buffer configuration, wherein a buffer segment is brought into the fluid flow path;

[0213] Figure 6a shows the extraction of solvent by a pump in a fluid system;

[0214] Figure 6b shows the steps of preparing the fluid system to prepare it for collecting the first fraction;

[0215] Figure 7a A first fraction is shown arriving at a detector located upstream in the fluidic system;

[0216] Figure 7b showing collecting a first fraction in a first collection reservoir using a fluid system;

[0217] Figure 8a The second fraction is shown arriving at the detector;

[0218] Figure 8b shows a fluid system in a buffer configuration, wherein a first fraction is being pushed through a buffer section before being collected;

[0219] Fig. 9 The washing of the buffer segment is shown to prepare it for subsequent collection;

[0220] Fig.10 showing collection of a second fraction in a second collection reservoir;

[0221] Fig.11 shows the fluidic system switching between collecting two fractions without using a buffer section; and

[0222] Fig.12 Collection of the second fraction without first using a buffer segment is shown;

[0223] Fig.13a -13b shows the ports and connections on the switching valve;

[0224] Fig.14a - 14c shows the fluid connection when the switching valve switches between the collection configuration and the discharge configuration; and

[0225] Fig.15a -15c shows the fluid connection when the switching valve is switched between the exhaust configuration and the buffer configuration. DETAILED DESCRIPTION

[0226] Figure 1 One embodiment of a fluid system 10 is shown, which can be a liquid chromatography system, preferably an HPLC system, which can be used to collect fractions eluted downstream of a detector 900. The detector 900 can be a UV detector that can detect the presence of components in a fluid flowing through it based on the absorption of light by the components in the fluid, or it can be another non-destructive detector, for example, other optical detectors. It will be understood that the fluid system 10 can be configured for use with other components of an HPLC system, which can include at least: a separation column 860 upstream of the detector 900; a sample storage section upstream of the separation column 860, such as a sample loop 870; and an analytical pump 850 that drives a mixture of solvent and sample from the storage section 870 through the separation column 860. In addition, the system can also include a unit 880 for introducing a sample into the system, such as a metering device 880 connected to a needle 890, which can be connected to a needle seat 895. Although for simplicity of illustration, these components are only shown in FIG. Figure 1 Although shown in the figures, those skilled in the art will appreciate that these components may also exist in the configurations shown in other figures.

[0227] The fluid system 10, which may also be referred to as a fraction collector, may also include a rotary valve 200 (which may be referred to as a fraction valve or a switching valve), which includes a plurality of ports (0 to 8, wherein the first port 0 is directly connected to the detector 900 via an inlet line and carries the mixture eluted from the separation column) and a plurality of connectors 210, which may be referred to as a first connector 210b, a second connector 210a, and a third connector 210c. Each connector 210 is configured to variably connect a plurality of ports of the valve 200. The system 10 also includes a waste reservoir 700 directly connected to the discharge port 3 and the waste port 5 of the valve. The system 10 may also include a pump 100 directly connected to the pump port 8 (which may flush the pump, or a container with pressurized gas, or a metering device), and a collecting device 300, which may include a collecting tube 320 and a collecting needle 310. The collecting device 300 may be directly connected to the second port 2. For example, the pump 100 may be configured to provide an operating pressure of 8 bar. It may also include an internal cavity that can store a cleaning / rinsing solvent. The volume of the internal cavity may be, for example, 1 ml. The illustrated system 10 also includes a cleaning section 600 that can be used to clean the collection needle 310 and a buffer section 400 that can be a buffer ring and is directly connected to the third port 4 and the fourth port 1 of the switching valve 200.

[0228] When it is mentioned that a component is directly connected to a port of the switching valve 200, this should mean a fluid connection between the component and the corresponding port of the switching valve 200, and there is no other port in the connection between the component and the corresponding port. Figure 1 In the configuration shown in , the detector 900 is directly connected to the first port 0. The two pieces are connected to each other, and there are no other ports in this connection. Figure 1 In the embodiment, the detector 900 is also connected to port 3, which may be referred to as exhaust port 3. However, the connection between the detector 900 and the exhaust port 3 is through the first port 0, that is, there is another port of the valve 200 in the connection, so that the connection is not a direct connection as used in this specification.

[0229] Further with respect to these figures, it is noted that in the figures shown, port 6 is not shown. Therefore, whenever ports 0 to 8 are mentioned, it is understood that port 6 is not on the switching valve. Alternatively, it may be present on the switching valve, but may not participate in the execution of the method described below.

[0230] The fluid system 10 further includes: a plurality of collection reservoirs 500 (500a, 500b, 500c), which may also be referred to as vials, which may be used to collect a plurality of fractions eluted from a separation column located upstream of the detector 900; and a solvent reservoir 50, which may include a solvent that may be used to clean the fluid system 10, such as the buffer section 400 or the fluid in the collection device 300. The collection needle 310 may be configured to be moved into one of the plurality of collection reservoirs 500 when needed. In an embodiment, the collection reservoirs 500 may be arranged in a one-dimensional or two-dimensional array, and the movement of the collection needle 310 may be appropriately configured. The solvent reservoir 50 may also be directly connected to the cleaning section 600 to provide a cleaning solvent for cleaning the outer surface of the connection needle 310.

[0231] The fluid system 10 may also include at least one flow sensor 800 (or multiple flow sensors). At least one of these flow sensors 800 may be installed on the waste line, i.e., upstream of the waste reservoir 700, and configured to measure the flow rate of the fluid flowing into the waste reservoir 700. This may help determine the time when the fraction to be collected reaches the collection needle 310 as follows: for example, at the beginning of the separation process, the delay volume (amount) of the fluid device connecting the outlet of the detector 900 to the collection needle 310 may be determined. Then, for example, based on the flow rate of the fluid discharged into the waste reservoir 700, the time required for the peak to travel to the collection needle 310 after washing out from the detector 900 may be determined. This will then represent, for example, an upper limit on the time required to accurately switch the switching valve 200 and bring the collection needle 310 to the empty collection reservoir 500 after the peak is detected in the detector 900.

[0232] The fluid system 10 may further comprise a control unit 60 configured to control the rotation of the rotor based on feedback from the flow sensor 800, wherein data connections are shown as dashed lines. This may allow switching the operating mode of the fluid system 10 to a suitable mode as further described below.

[0233] The control unit 60, which may also be referred to as the controller 60, is operatively connected to other components, such as Figure 1 More specifically, the controller 60 is operably connected to the valve 200 (more specifically, its rotatable driver), the sensor 800, the pump 100, the metering device 880 (more specifically, the stepper motor of the metering device 880), and the collection device 300.

[0234] The controller 60 may include a data processing unit and may be configured to control the system and perform specific method steps. The controller may send or receive electronic signals of instructions. The controller may also be referred to as a microprocessor. The controller may be contained on an integrated circuit chip. The controller may include a processor with a memory and associated circuits. A microprocessor is a computer processor that has the functionality of a central processing unit on a single integrated circuit (IC), or sometimes up to multiple integrated circuits, such as 8 integrated circuits. A microprocessor may be a multi-purpose, clock-driven, register-based digital integrated circuit that accepts binary data as input, processes it according to instructions stored in its memory, and provides results (also in binary form) as output. A microprocessor may include combinational logic and sequential digital logic. A microprocessor operates on numbers and symbols represented by a binary number system.

[0235] Although the controller 60 is only Figure 1 , but it should be understood that the controller is typically present when the system presents other configurations shown in other figures.

[0236] Furthermore, the fluid system 10 may also be configured to be used together with a computer program product, which may include instructions for causing the control unit to switch the switching valve 200 and / or move the collecting needle 310 to above a designated collecting reservoir 500 .

[0237] Figure 1 Also shown is a configuration of the fluid system 10 in which the second connector 210a connects ports 1 and 8, the first connector 210b connects ports 0 and 3, and the third connector 210c connects ports 4 and 5. Figure 1 The configuration shown in may represent a typical setup in a chromatographic separation process without a fraction collector, wherein the fluid is sent to a waste reservoir 700 after being analyzed in the detector 900. In this configuration, no eluate is collected in the collection reservoir 500. Because the waste reservoir 700 may have been used to collect fluids from previous steps in the separation process, including, for example, steps of washing and equilibrating the separation column, the mixture collected in the waste reservoir 700 may not be suitable for further analysis. Therefore, if the eluted fractions are to be further analyzed, it may be advantageous to provide a separate fraction collection procedure (i.e., a procedure for collecting each distinct fraction of the sample into a different reservoir).

[0238] It may also be noted that the Figure 1 The flushing solvent for distributing the remaining liquid in the collection device 300 and the collection needle 310 shown in the figure can be the mobile phase for the fluid system (which may be an HPLC system) or an additional cleaning solvent prepared by the user. Additional cleaning / cleaning solvent can also be used to prime the pump 100 before each sample injection.

[0239] So, in other words, Figure 1 The fluid system 10 shown in the figure may include a fraction collection system, which may be referred to as a fraction collector. The fluid system 10 may include: a multi-port rotary valve, or a switching valve 200, which may also be referred to as a fraction valve; a flow sensor 800 (or multiple flow sensors), which is installed on the waste line leading to the waste reservoir 700; a pump 100; a collection device 300, which includes a collection needle 310 and a collection tube 320; and its cleaning section 600; and a buffer section 400.

[0240] The object of the present invention is to use Figure 1 The additional components shown in the diagram, namely the switching valve 200, the buffer section 400 and the collection reservoir 500, provide a robust method for collecting fractions downstream of the detector 900. An embodiment of the method will now be described and how the illustrated configuration can be used to collect a variety of fractions.

[0241] Figure 2a An exemplary design of a switching valve 200 is shown. It may include a static part, which may be referred to as a stator, which includes a plurality of ports 0 to 8 that are directly connected to other components of the fluid system 10 described above. Figure 2a As shown in , multiple ports 0 to 8 can be positioned on the stator in a circular arrangement.

[0242] The switching valve 200 may also include a rotating section, which may be referred to as a rotor, which may include a plurality of connectors 210, for example, three connectors 210a, 210b, 210c, which are configured to provide fluid connections between the ports of the stators to which they are respectively connected. For example, the connectors may be positioned on the rotor, such as Figures 2b to 2d as shown in . Figures 2b to 2d The dotted line in the Figure 2a , the portion of the switching valve 200 which is hidden from view is shown in FIG. 1 , wherein the rotor is attached below the stator.

[0243] The rotor may be configured to rotate about an axis perpendicular to the plane of the rotor and passing through its center. The angle at which the rotor is allowed to rotate may be determined by the relative positions of connector 210 and ports 0 to 8. For example, Figure 2c -2d, the rotor can be constructed relative to Figure 2b The discharge configuration shown in FIG. 1 is rotated ±45°, wherein the second connector 210a is shown as connecting ports 1 and 8, the first connector 210b is shown as connecting ports 0 and 3, and the third connector 210c is shown as connecting ports 4 and 5. It should be noted that this is also Figure 1The configuration shown in . The rotation angle can be selected between 10° and 80°, preferably between 20° and 70°, and more preferably between 30° and 60°. A smaller rotation angle allows the rotor to rotate quickly, thereby improving the efficiency of the fractionation process.

[0244] Figure 2c -2d also shows two additional configurations of the rotor. Figure 2c The collection configuration of the rotor is shown, wherein the second connector 210a connects ports 7 and 8, the first connector 210b connects ports 0 and 2, and the third connector 210c connects ports 3 and 4. This configuration can be achieved by, for example, placing the rotor from Figure 2b The emission configuration shown in is obtained by rotating -45°.

[0245] Figure 2d Another configuration is shown in FIG. 1 , which may be referred to as a buffer configuration, which is achieved by moving the rotor from a discharge configuration (see Figure 2b ) is rotated +45°. In this configuration, the second connector 210a connects ports 1 and 2, the first connector 210b connects ports 0 and 4, and the third connector 210c connects port 5 to the dead end port (dead port), that is, stops the flow into port 5 (stops the flow into port 5).

[0246] In the illustrated embodiment, the connectors 210a, 210b, and 210c are shown as having a specific shape. Figures 1 to 2d It will be appreciated that the first port 0 may be at the center of the valve 200 and the other ports 1 to 8 may be arranged on a ring or circle and at the same distance from the central port 0. The first connector 210b may generally be configured to connect the central port 0 with one of the circumferential ports 1 to 3, and the second connector 210a and the third connector 210c may be configured to connect two of the circumferential ports 1 to 8.

[0247] In the illustrated embodiment, the first connector 210b is shown as a hook. That is, it includes a straight section and an arc section. However, it will be understood that this is just an example, and the first connector can also be implemented in other ways, for example, it can only include a straight section.

[0248] In addition, the second connector 210a and the third connector 210c are shown as being arc-shaped. Again, it should be understood that this is merely exemplary and they may also be of different shapes (eg, they may be straight).

[0249] Furthermore, as shown in the figure, the circumferential ports 1 to 7 may preferably be located equidistant from each other (except ports 5 and 7). Figure 1As shown in FIG. 1 , connector 210 can establish connections between various ports without dead volume. See, for example, connector 210 b connecting ports 0 and 3 without dead volume and connector 210 c connecting ports 4 and 5 without dead volume. In addition (although in FIG. 1 ), connector 210 can establish connections between various ports without dead volume. Figure 1 ), this is also possible for connector 210a, which can also be sized to allow dead-volume-free connection of the various ports.

[0250] In other words, the switching valve 200 can be used in the fluid system 10 for fraction collection. It can be embedded in the HPLC system, for example, by high-speed switching in the three operating configurations / positions described above, to direct the HPLC system flow to the waste reservoir 700, the collection reservoir 500 or the buffer section 400 (when the fluid system 10 is still connected to the collection reservoir 500), the three operating configurations / positions are: the discharge configuration ( Figure 2b ) (also called waste location), collection configuration ( Figure 2c ) and buffer configuration ( Figure 2d ) (also referred to as a flushing position). Thus, the use of the buffer section 400 may enable an additional "flushing" step to be achieved by the switch valve 200 as part of the fluid system 10 described above. The discharge configuration may preferably be located between the collection configuration and the buffer configuration. This may help reduce carryover. The placement of the switch valve 200 in the fluid system 10 for these configurations is also Figure 3 (Emission Configuration), Figure 4 (collection configuration) and Figure 5 (Buffer Configuration) is shown.

[0251] Figure 3 FIG. 1 shows a configuration of the fluid system 10 in which the switching valve 200 is in the above-mentioned exhaust configuration. Figure 3 and Figure 1 When making a comparison, those skilled in the art will understand that Figure 1 In the embodiment, port 5 is connected to waste 700, port 3 is also connected to the waste 700, and Figure 3 Port 5 is shown connected to waste 700, but this waste is different from the waste 700 to which port 3 is connected. However, it should be understood that this is interchangeable, that is, in the same Figure 3 In FIG. 5 , port 5 can be connected to the waste material 700 to which port 3 is connected (this also applies to the subsequent figures). In addition, for the sake of simplicity, in Figure 3 The connection between the solvent reservoir 50 and the cleaning port 600 is shown in a simplified manner in the following figures. Figure 3 As shown in FIG. 4 , port 4 is connected to waste 700. However, the line downstream of port 5 also has a junction upstream of waste reservoir 700. Thus, port 5 may be connected not only to waste reservoir 700, but also to purge port 600 (e.g., via a two-way valve).

[0252] In this configuration, the eluate from the detector 900 is discharged into the waste reservoir 700, and the pump 100 can be used to simultaneously fill the buffer section 400 with a cleaning solvent, which may be drawn from the solvent reservoir 50 in the previous step. More specifically, the pump 100 can cause the flow (amount) to pass through port 8, port 1, the buffer section 400, port 4 and port 5 toward the waste reservoir 700. However, as described, there may also be a valve (e.g., a two-way valve) in the connection between port 5 and the waste reservoir 700. Through the valve, the fluid flow can also be directed to the cleaning port 600 and the waste reservoir, and the waste reservoir is also connected to port 3. Therefore, the solvent flowing through the buffer section 400 can also be used to clean the cleaning port 600.

[0253] This may allow the buffer section 400 to be ready for a subsequent step, wherein fractions eluted from the separation column upstream of the detector 900 may be collected in one of the collection reservoirs 500 via the buffer section 400 .

[0254] Figure 4 The fluid system 10 is shown in a collection configuration using the switching valve 200 described above. In this configuration, the collection needle 310 can be moved from the cleaning section 600 to one of the collection reservoirs 500, such as 500a, where the fractions washed out from the separation column can be collected. It is noted that ports 7 and 8 can also be connected in this configuration, which allows the pump 100 to be filled with solvent from the solvent reservoir 50 after being emptied into the buffer section 400 in a previous step, for example.

[0255] Figure 5 The fluid system 10 is shown with a buffer configuration using the switching valve 200 described above. This configuration may be used when the fluid system 10 is used to collect fractions eluted at relatively short intervals in time. For example, in order to prevent a first eluted fraction from being contaminated by a second eluted fraction, the buffer section 400 may be used to include a buffer for separating different fractions. As will be appreciated by those skilled in the art, Figure 5 In the configuration shown in FIG, detector 900 is fluidically connected to port 0, but there is no fluid connection between detector 900 and port 5. Figure 5 , the line connecting detector 900 and port 0 appears to be in contact with connector 210c, but it will be understood that the line and connector 210c are actually offset from each other in a direction perpendicular to the plane of the drawing, and there is actually no connection between these parts.

[0256] Now refer to Figures 6a to 12 A typical operation flow of using the above fluid system 10 to collect two fractions is described.

[0257] In a first preparatory step, which can be carried out before the separation begins, e.g. Figure 6aAs shown in FIG. 6b, the fluid system 10 can be used to clean the buffer section 400 and the collection needle 310. Turn the switching valve 200 to Figure 2c To perform the cleaning process, as shown in the collection configuration shown in FIG. Figure 6a As shown in , the cleaning / washing solvent is drawn into the pump 100. Here, the second connector 210a connects ports 7 and 8, which allows fluid flow from the solvent reservoir 50 to enter the pump 100. The pump 100 may include a piston and a housing, and drawing the solvent may include: actuating the piston to reduce the pressure within the pump 100. This is also Figure 6a Shown in.

[0258] Figure 6a Also shown is a first connection 210b connecting ports 0 and 2 of the switching valve 200. Thus, fluid injected into the inlet line from the detector 900 flows into the cleaning section 600. Since this step can be performed before the separation process begins, the injection from the detector 900 may not be present or only include solvent. The cleaning section 600 may also be configured to draw solvent from the solvent reservoir 50 so that the outer surface of the collection needle 310 can be cleaned at the same time. This can help remove traces of previously collected fractions from the outer surface of the collection needle 310.

[0259] Once the solvent has been drawn into the pump 100, it can be pushed into the buffer section 400. Figure 6b The switching valve 200 can be switched from its Figure 6a The position in the figure is rotated by +45° so that the second connector 210a now connects ports 1 and 8, the first connector 210b now connects ports 0 and 3, and the third connector 210c now connects ports 4 and 5. This corresponds to Figure 2b In this configuration, a fluid flow path is established between the pump 100 and the buffer section 400, and the other port of the buffer section 400 is connected to the waste reservoir 700. The solvent drawn into the pump 100 in the previous step can now be pushed into the buffer section 400. In this configuration, the ejection from the detector 900 can be directly introduced into the waste reservoir 700.

[0260] The volume of the pump 100 can be selected to be large enough so that the buffer section 400 is reliably filled with solvent at the end of the above-mentioned pumping process. Alternatively, if the volume of the pump 100 is not large enough, the above-mentioned steps of drawing in the solvent and pushing it into the buffer section 400 can be repeated until the buffer section 400 is filled with solvent.

[0261] After filling the buffer section 400, the pump 100 may be filled with solvent from the solvent reservoir 50 for use in a subsequent flushing process. This may help improve the efficiency of the collection process and may be advantageous when multiple closely spaced fractions may be collected. In addition, the above process of cleaning and filling the buffer section 400 and filling the pump 100 may be repeated after each fraction is collected. This also helps to avoid contamination of any fraction with components from other fractions.

[0262] like Figure 6a and 6b As further shown, the collection needle 310 can remain in the cleaning section 600 throughout the process of preparing the fluid system 10 for fractionation. Figure 7a and 7b As shown in , the fluid system 10 can now be used to collect the first fraction.

[0263] in other words, Figure 6a and 6b The steps shown in the figure can be summarized as filling the pump 100 and the buffer section 400 with a cleaning / cleaning solvent, while cleaning the outer surface of the collecting needle 310. These steps may include pumping the solvent into the cavity of the pump 100 and filling the inner cavity of the pump 100 with a cleaning / cleaning solvent. At the same time, the buffer section 400 may also be filled with a cleaning / cleaning solvent. This may include distributing the liquid into the waste reservoir 700 and filling the buffer section 400. It should be noted that the above steps may also be repeated multiple times to fill the solvent into the pipeline (which connects the solvent reservoir 50 to the pump 100), thereby completing the startup task of the pump. At the same time, the outer surface of the collecting needle 310 may also be cleaned. Once these are completed, the pump 100 is ready for the subsequent buffer section cleaning function. When the buffer section is used to realize fraction collection, this filling process of the pump 100 can be performed each time before cleaning the buffer section 400.

[0264] Figure 7a The fluid system 10 is shown in the fraction collection mode. The switching valve 200 can be left in the discharge configuration until the first fraction to be collected, shown as a straight black arrow, is detected in the detector 900 and triggers the collection needle 310 to move from the cleaning section 600 to one of the plurality of collection reservoirs 500, for example, to the first collection reservoir 500a. In addition, the switching of the switching valve 200 can also be triggered. The switching valve 200 can be switched to Figure 2c The collection configuration shown in FIG. 5 is used to establish flow between ports 0 and 2, which allows the first fraction to be collected in collection reservoir 500a, as shown in FIG. Figure 7b It is noted that an accurate estimate of the time required for any fraction to flow from the detector 900 to the collection needle 310 may be particularly advantageous in the above process.

[0265] Positioning the ports on the switching valve 200 so that the collection configuration of the switching valve 200 is between its discharge configuration and buffer configuration allows for rapid switching from the discharge configuration to the collection configuration by simply rotating the rotor of the switching valve 200 by 45°. When collecting fractions with the switching valve 200 in the collection configuration, the pump 100 may not be operated. This may involve, for example, not actuating the piston of the pump 100 in the case where the pump 100 includes a piston. Collection of the first fraction continues until the second fraction that may be collected reaches the detector 900.

[0266] The fluid system 10 can now be switched to the buffer configuration. For an explanation of the function of the buffer configuration, reference is again made to Figure 7b On the right side of the figure, an exemplary sample composition diagram is shown as 1000. 1000 shows the sample composition between point 1002 and collection needle 310 (see Figure 7b ). In this figure, the vertical axis is related to the position between point 1002 (corresponding to the top of the figure) and the collection needle 310 (corresponding to the bottom of the figure). The sample composition is shown vertically thereto, wherein at the bottom of the figure (corresponding to the collection needle 310), there is 100% of the first sample component, at the top of the figure (corresponding to point 1002), there is 100% of the second sample component, and the sample composition gradually changes from the middle point (corresponding to port 2) and the top of the figure. That is, at a certain point in time, such a sample composition may exist in the fluid system 10, wherein at point 1002, there is 100% of the second sample, and it decreases to about 0% at the middle point of port 2. That is, at port 2 (and downstream thereof), there may be 100% of the first sample component 1006, and at point 1002 (and upstream thereof), there may be 100% of the second sample component 1008. However, between point 1002 and port 2, the sample composition may gradually change between these sample components.

[0267] Reference again Figure 7b , when collecting fractions until Figure 7b At the time point of , only the first sample component 1006 will be collected in the first collection reservoir 500a. However, if the system continues to operate in this configuration, the second sample component 1008 will also be collected in the first collection reservoir 500a, which may be undesirable.

[0268] However, if the system is directly switched to collect sample in another collection reservoir (eg, in the second collection reservoir 500b), mixed sample components will also be collected.

[0269] therefore, Figure 7a and 7bThe above steps shown in can be summarized as follows. The collection needle 310 can be moved to the first collection reservoir 500a. The fluid system 10 can remain idle in the discharge configuration until the first target fraction arrives. When the collection time window begins, the switching valve 200 can be switched to the collection configuration so that the first fraction is collected in the first collection reservoir 500a until the second target fraction arrives. The first target fraction is distributed to the first collection reservoir 500a through the collection tube 320 and the collection needle 310. At this time, for example, the pump 100 is "closed", that is, it is switched to zero flow without actuating the piston.

[0270] For example, to avoid this situation, the system 10 may switch to Figure 8a . Thus, the solvent in the buffer section can be used as a separator that separates the pure component 1006 (which is present at port 2 and downstream thereof when switching) from the mixture of components 1006 and 1008. Therefore, the pure component 1006 present in this section can still be forced into the first collection reservoir 500a under this configuration without the risk of component 1008 also being collected in this collection reservoir 1008 (because there is now a buffer solvent 1010 upstream of component 1006).

[0271] same, Figure 8a This is further illustrated in the diagram 1000′ in FIG. Figure 8a In the configuration shown in FIG. 1 , there is solvent and sample between port 4 and collection device 300. It is noteworthy that between port 2 and collection device 300, there is sample component 1006, and upstream thereof between port 4 and port 2, there is buffer solution 1010. When the system continues to be operated in this configuration, sample component 1006 will be further collected in reservoir 500a until the buffer solution reaches collection device 300 - see FIG. Figure 8b , the diagram 1000 ″ here corresponds to the diagram 1000 ′. That is, in this configuration, in the upstream section of the collection device 300 , there will be a buffer solution, and further upstream there will be a section containing the mixture of 1006 and 1008 .

[0272] The system can then switch to Fig. 9 The configuration shown in , thus allowing the mixing section to be (rinsed) out of the system to reach a state where pure sample components 1008 are present at port 3 (and upstream thereof). One can then switch the system to Fig.10 In the configuration shown in FIG. 5 , the sample component 1008 is collected in the second collection reservoir 500 b. In this regard, it is also possible to present Fig.10Prior to the exact configuration shown in FIG. 1 , the collection device 300 is positioned in the cleaning section 600, as this allows the buffer solution initially present between port 2 and the collection device 300 to be drained. That is, this configuration may be maintained until a pure sample component 1008 is present in the collection device 300 (and upstream thereof), and then the system may be switched to Fig.10 , so that the pure sample component 1008 can be collected in the collection reservoir 500b, as shown in Fig. 9 As shown in .

[0273] In other words, from Figure 7b Starting with the configuration shown in , the system 10 may switch to Figure 8a The configuration shown in the figure is used to switch the buffer section 400 into the pipeline. More specifically, the switching valve 200 can be rotated by +90° to achieve Figure 2d . This may allow the buffer section 400 to be introduced into the flow path so that the first fraction that may still flow out of the inlet line into the fluid system 10 may be introduced into the collection reservoir 500a through the buffer section 400. As described above, the buffer section 400 may have been filled with a cleaning / rinsing solvent in a previous step so that the first fraction is not contaminated when flowing through the buffer section 400. The advantage of the buffer section 400 may be to prevent mixing of the first fraction and the second fraction that will be collected. This may be achieved in the following way.

[0274] The switching valve 200 may remain in its buffer configuration until all of the first fraction has been dispensed into the collection reservoir 500a. Again, this time may be determined by the duration of the peak of the first fraction and the time required for the peak to flow to the collection needle 310 (including the volume of the buffer section 400). It is also noted that some portion of the second fraction may flow into the buffer section 400 until the first fraction has been completely dispensed into the collection reservoir 500a (see Figure 8b 1000” in the figure). Therefore, at this time, the buffer section 400 may be partially filled with the first fraction, the second fraction and the solvent (mobile phase).

[0275] In other words, when the second fraction arrives, the switching valve 200 is switched to the buffer section configuration and the first fraction is continued to be collected through the buffer section 400. That is, before the second target fraction flows into the collection tube 320, the switching valve 200 is switched to the buffer configuration, thereby allowing the fluid system 10 to keep the remaining first target fraction in the collection tube 320 and the collection needle 310 being pushed through the pre-filled clean solvent in the buffer section 400. Therefore, the buffer section 400 is used to prevent mixing between the first target fraction and the second target fraction. Keep this configuration until all the first target fractions are distributed into the first collection reservoir 500a. At this time, the buffer section 400 can be almost completely filled with the first fraction, the second fraction and the solvent (mobile phase). The buffer configuration can help to improve the recovery rate of the first target fraction. At the same time, the buffer section 400 can be used to prevent mixing between the first target fraction and the second target fraction, thereby reducing the carryover (residue).

[0276] Once the collection of the first fraction is complete, the switching valve 200 can be switched again, this time to Figure 2c This brings the fluid system 10 to Fig. 9 The configuration shown in .

[0277] The first connector 210b can now connect ports 0 and 3, thereby allowing some of the second fraction to flow into the waste reservoir 700. At the same time, the pump 100 can now be brought into fluid connection with one port of the buffer section 400, while its other port can be connected to the waste reservoir 700. The buffer section 400 can now clean the mixture of solvent and the first and second fractions, which may be left over from the previous collection step, by pushing the solvent stored in the pump 100. The clean solvent can flow into the buffer section 400, while the mixture of the first and second fractions and the solvent is pushed out into the waste reservoir 700. This can be achieved by actuating the piston of the pump 100. In addition, for example, Fig. 9 As shown, the collection needle 310 can be moved to the second collection reservoir 500b. This can prepare the fluid system 10 to collect the second fraction.

[0278] Fig.10 FIG. 5 shows a configuration of a fluid system 10 for collecting a second fraction in a second collection reservoir 500b. In addition to the difference in the collection reservoir, this configuration can be similar to Figure 7b The configuration for collecting the first fraction shown in is basically similar. The switching valve 200 can be switched back to Figure 2c , and the second fraction flows into the collection reservoir 500b via the entry line, the first connection 210b and the collection device 300. If an additional third fraction is to be collected, the buffer section 400 can be connected to the flow path again and used for collection without any mixing of the fractions.

[0279] In other words, after completing the collection of the first fraction through the buffer section 400 as described above, the switching valve 200 can be switched to the discharge configuration, in which a portion of the second target fraction flows into the waste reservoir 700. During this period, the pump 100 can be actuated to push the liquid mixture in the buffer section 400 into the waste reservoir 700 and refill it with a clean solvent from the cavity of the pump 100. At the same time, the collection needle 310 can move to the next collection reservoir 500b. Then, the switching valve 200 can be switched back to the collection configuration to distribute the second fraction into the second collection reservoir 500b without any mixing and without carryover.

[0280] This allows the entire process of fraction collection to be completed with the intermediate buffer configuration enabled.

[0281] Fig.11 and 12 1 shows an alternative configuration of the fluid system 10 described above, wherein the collection reservoir can be switched from 500a to 500b to collect the second fraction without including an intermediate buffer configuration of the purge buffer section 400. Fig.11 As shown in FIG. 5 , once the first fraction has been collected in the collection reservoir 500a, the switching valve 200 may be moved to the discharge configuration (see FIG. 5 ). Figure 2b ), similar to Figure 7a , but without operating the pump 100 to push the solvent into the buffer section 400. Thereafter, the collection needle 310 can be moved from the collection reservoir 500a to the collection reservoir 500b.

[0282] Note that this is different from the above process, in which, after partially collecting the first fraction, the switching valve 200 is switched to a buffering configuration that introduces the buffer section 400 into the flow path. This involves rotating the switching valve 200 by +90°. Instead, it may be more efficient to skip the buffering configuration and only rotate the switching valve 200 by -45° to bring it into the collecting configuration (see Figure 2c ).

[0283] Therefore, if Fig.12 As shown in , once the connection needle 310 is accommodated in the collection reservoir 500b, the switching valve 200 is rotated to the collection configuration, which can bring the inlet line to direct connection with the collection device 300 so that the second fraction can flow into the collection reservoir 500b. Since the buffer section 400 is not used in this embodiment, it may not be necessary to fill the pump 100 with a solvent or to clean the buffer section 400 before the collection process.

[0284] In other words, in the case of a non-buffered configuration, the pump 100 can remain stationary all the time. When the target fraction is reached, the fluid system 10 triggers collection. The switching valve 200 switches between two configurations at high speed: the collection configuration (see Fig.11) and emission configuration (see Fig.12 ). This can include job flows with no buffer configuration.

[0285] However, using these configurations for the collection process may involve a large amount of the first fraction and the second fraction flowing into the waste reservoir 700. This is because the collection of the first fraction may have to be terminated early and the switching valve 200 switched from the collection configuration to the waste reservoir 700. Fig.11 , in order to prevent the second fraction from flowing into the reservoir 500a. Similarly, in order to reliably ensure that once the switching valve 200 moves to Fig.12 , the second fraction flows into the reservoir 500b, and a certain amount of the second fraction can be allowed to flow out into the waste reservoir before switching the switching valve 200 back to the collection configuration. The advantage of the above-mentioned buffer section 400 can be to allow such switching without a large amount of the first fraction or the second fraction being discharged into the waste reservoir 700.

[0286] exist Figures 13a to 15c An exemplary embodiment of a switching valve 200 is shown in FIG. Fig.13a An exemplary embodiment of a rotor 210 of a switching valve 200 is shown. As described above, the rotor 210 may include connectors 210a, 210b, and 210c, which may be implemented as grooves. The connector 210b may be an L-shaped groove, which includes a long section 210b1 and a short section 210b2. The section 210b1 may also be referred to as a radial section 210b1, and the section 210b2 may also be referred to as a circumferential section 210b2. The connectors 210a and 210c may be located on both sides of the groove 210b. The long section 210b1 may be substantially parallel to the radius of the switching valve 200, and the short section 210b2 may be substantially parallel to the arc section of the switching valve 200. The connectors 210a and 210c may also be substantially parallel to the arc section of the switching valve 200. The L-shaped connector 210b and the slot labeled angle A may be particularly beneficial for reducing back pressure spikes and continuing flow when the switching valve 200 switches from one configuration to the next.

[0287] Fig.13b 2 shows an exemplary embodiment of an arrangement of ports 0 to 8 on a stator of a switching valve 200 that can be configured to cooperate with a rotor 210. The stator may include a plurality of ports 0 to 8, which may be implemented as holes or slots on the stator. Fig.13b As shown in , ports 1 to 8 may be arranged in a circle on the stator. Also shown are two small grey slots 220a, 220b, which are connected to the second port 2 and the exhaust port 3, respectively. It may also be particularly beneficial to reduce back pressure spikes and continue flow when the switching valve 200 switches from one configuration to the next, as will now be described.

[0288] Fig.14a -14c shows the switching valve 200 from the collection configuration ( Fig.14a )Switch to the emission configuration ( Fig.14c ) is an exemplary state sequence of the switching valve 200 (or the connection state of each groove). As described above, Fig.14a In the collection configuration shown in FIG. 1 , ports 0 and 2 are fluidically connected to each other so that the fraction eluted from the upstream separation process is collected in the collection reservoir 500 connected to the second port 2. Then, in order to collect the second fraction, the fluid system 10 can be switched to Fig.14c , where the first port 0 and the exhaust port 3 may be fluidly connected. This may involve rotating the rotor 210 counterclockwise. Fig.14b As shown in FIG. , in the rotor 210 from the collection configuration ( Fig.14a ) counterclockwise to discharge configuration ( Fig.14c ), the flow from the first port 0 can always be fluidly connected to the second port 2 or the exhaust port 3. Therefore, in this transition, the first port 0 is always fluidly connected to another port.

[0289] Therefore, flow from port 0 may not be blocked and back pressure spikes may not be introduced. For example, by selecting the length of the slot on the second port 2 (in Fig.13b This is particularly advantageous in that the short section 210b2 of the connecting member 210b of the rotor 210 and the slot of the second port 2 can span the length of the rotor 210 between ports 2 and 3, such as Fig.14b Thus, when switching between the collection configuration and the discharge configuration, the fluid connection between ports 0 and 2 is severed, and the fluid connection between ports 0 and 3 is established.

[0290] Fig.15a -15c shows the switching valve 200 from the exhaust configuration ( Fig.15a )Switch to buffered configuration ( Fig.15c ) is an exemplary state sequence of the switching valve 200 (or the connection state of each groove). Fig.14a -14c is similar to the switching shown in FIG. 14c, when the rotor 210 is changed from the discharge configuration ( Fig.15a ) counterclockwise to buffer configuration ( Fig.15c ), the flow from the first port 0 can always be connected to the exhaust port 3 or the third port 4. Therefore, the flow from port 0 may not be blocked and no back pressure spike will be introduced. Similarly, by, for example, selecting the length of the slot on the exhaust port 3 (in Fig.13b This is particularly advantageous in that the short section 210b2 of the connecting member 210b of the rotor 210 and the slot of the discharge port 3 can span the length of the rotor 210 between ports 3 and 4, as shown in FIG. Fig.15bThus, when switching between the exhaust configuration and the buffer configuration, the fluid connection between ports 0 and 3 is cut off, and the fluid connection between ports 0 and 4 is established.

[0291] It will be understood that reference Figures 13a to 15c The valve 200 described may be used with reference to Figures 1 to 12 However, those skilled in the art will appreciate that reference Figures 13a to 15c The valve 200 described may also be used independently of the reference Figures 1 to 12 Described systems and methods for use.

[0292] Therefore, in general, embodiments of the present technology, particularly for the collection of closely arranged fractions / peaks and very small volume fractions, allow for efficient collection of fractions with higher recoveries and less or almost no carryover by adopting a buffer configuration (flushing out or distributing residual liquid in the collection tube 320 and the collection needle 310 to improve recovery and reduce carryover).

[0293] Whenever relative terms such as "about", "substantially" or "approximately" are used in this specification, the terms should also be interpreted as also including the exact terms. That is, for example, "substantially straight" should be interpreted as also including "(completely) straight".

[0294] Whenever a step is described above or also in the appended claims, it should be noted that the order of the steps described herein may be accidental. That is, unless otherwise specified or unless it is clear to a person skilled in the art, the order in which the steps are described may be accidental. That is, when it is stated herein, for example, that the method comprises steps (A) and (B), this does not necessarily mean that step (A) precedes step (B), but it is also possible that step (A) and step (B) are (at least partially) performed simultaneously, or that step (B) precedes step (A). In addition, when step (X) is said to be before another step (Z), this does not mean that there are no steps between steps (X) and (Z). That is, step (X) before step (Z) covers the case where step (X) is performed immediately before step (Z), and also covers the case where step (X) is performed before one or more steps (Y1), ... and then step (Z). When using terms such as "after" or "before", corresponding considerations also apply.

[0295] Although preferred embodiments have been described above with reference to the accompanying drawings, those skilled in the art will appreciate that these embodiments are provided for illustrative purposes only and should in no way be construed to limit the scope of the present invention defined by the claims.

Claims

1. A fluid system, wherein: The fluid system comprises: A switching valve, the switching valve comprising a plurality of ports, wherein the switching valve is configured to connect the ports in different configurations, wherein the ports comprise a first port (0) and a second port (2); an inlet line, the inlet line being directly connected to the first port (0); A detector (900), the detector (900) being located upstream of the switching valve; a collecting device (300), the collecting device being directly connected to the second port (2), the collecting device comprising a collecting needle (310); A first collection reservoir (500a); and a second collection reservoir (500b); wherein the fluid system is configured to be in a collection configuration, wherein the first port (0) and the second port (2) are connected, and wherein the collection needle (310) moves to one of the first collection reservoir (500a) and the second collection reservoir (500b), the first collection reservoir (500a) collects a first target fraction, and the second collection reservoir (500b) collects a second target fraction; Wherein, the ports include a third port (4) and a fourth port (1); Wherein, the fluid system comprises a buffer section (400), the buffer section being directly connected to the third port (4) and the fourth port (1); The fluid system is configured in a buffer configuration, wherein the first port (0) is connected to the third port (4), and the fourth port (1) is connected to the second port (2); and wherein the switching valve is configured to switch to the buffer configuration when the second target fraction reaches the detector (900); wherein the ports include a pump port (8) and a waste port (5) directly connected to waste; Wherein, the fluid system comprises a pump (100), the pump being directly connected to the pump port (8); The fluid system is configured to be in a buffer zone cleaning configuration, wherein the pump port (8) is connected to the fourth port (1), and the third port (4) is connected to the waste port (5).

2. The fluid system according to claim 1, characterized in that The switching valve includes a first connection member for connecting to the port.

3. The fluid system according to claim 2, characterized in that The first connection member connects the first port (0) and the second port (2) in the collecting configuration.

4. The fluid system according to claim 1, characterized in that: The ports include a discharge port (3), wherein the switching valve comprises a stator, wherein the stator comprises the plurality of ports; wherein the switching valve comprises a rotor, wherein the rotor comprises at least one connector for connecting the ports in different configurations, wherein the at least one connector is at least one slot; wherein the rotor includes a slot connected to the second port and extending between the second port and the exhaust port; wherein the switching valve is configured in a collecting configuration to fluidly connect the first port and the second port; wherein the switching valve is configured in a discharge configuration to fluidly connect the first port and the discharge port; The switching valve is configured to transition from the collecting configuration to the discharging configuration so that the first port is always connected to the second port or the discharging port during the transition period.

5. A method of operating a fluid system, the fluid system being the fluid system according to claim 1, wherein: The method comprises: The fluid system is in the collecting configuration, and the fluid flow enters the first collecting reservoir through the inlet line, the first port (0), the second port (2) and the collecting device (300) in the collecting configuration; The fluid system is placed in the buffer configuration, and the second fluid flow is caused to flow through the inlet pipeline, the first port (0), the third port (4), the buffer section, the fourth port (1), the second port (2) and the collection device in the buffer configuration; and After the fluid system is in the buffer configuration, the fluid system is in the buffer section cleaning configuration, and the fluid system allows the cleaning flow to pass through the pump port (8), the fourth port (1), the buffer section, the third port (4), the waste port (5) and flow to the waste under the buffer section cleaning configuration.

6. The method according to claim 5, It is characterized in that The second fluid flow causes fluid to flow into the first collection reservoir.

7. The method according to claim 5, characterized in that The method further comprises: After the fluid system is in the buffer section cleaning configuration, the fluid system is again in the collection configuration, and the fluid system allows the fluid flow to enter the second collection reservoir through the inlet pipeline, the first port (0), the second port (2) and the collection device in the collection configuration.

8. A computer program product, characterized in that The computer program product comprises instructions which, when executed on a control unit of a fluid system, are configured to cause the fluid system to perform the method according to claim 5 .

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