Valve for transferring at least one fluid

Abstract

A valve (110) for transferring at least one fluid is disclosed. The valve comprises: - at least one stator (112), wherein the stator (112) comprises a plurality of ports (118), the ports (118) comprises a plurality of groups (122) of ports (118), the plurality of groups (122) of ports (118) comprises a first group (124) of at least two first ports (126), a second group (128) of at least two second ports (130), and a third group (132) of at least two third ports (134); - at least one rotor (114), wherein the rotor (11 4) comprising a plurality of channels (144), the channels (144) comprising at least one first channel (146) and at least one second channel (148); and at least one actuator (116), wherein the actuator (116) is operably connected to the rotor (114); wherein the actuator (116) is configured to rotate the rotor (114) into at least one loading orientation (180), wherein in the loading orientation (180) one or both of the following conditions exist: a) the first channel (146) connected to the first port (126) so that the first fluid (182) can be transferred into the first channel (146) via at least one of the first ports (126); b) the second channel (148) is connected to the second port (130) so that the second fluid (184) can be transferred into the second channel (148) via at least one of the second ports (130); wherein the actuator (116) is further configured to rotate the rotor (114) into at least one first injection orientation and at least one second injection orientation, wherein in the first injection orientation, the first channel (146) is connected to the third port (134) and the first fluid (182) can be transferred from the first channel (146) to at least one of the third ports (134), wherein in the second injection orientation, the second channel (148) is connected to the third port (134) and the second fluid (184) can be transferred from the second channel (148) to at least one of the third ports (134).

Description

Technical Field

[0001] The present invention relates to a valve for transferring at least one fluid, an analytical system for analyzing a sample, a method for transferring at least one fluid and the use of a valve. The device and method according to the present invention can be used in particular for multidimensional separation of samples and chemical characterization of molecules. In particular, the device and method according to the present invention can be applied in the field of bioanalysis, in particular in the field of protein analysis. Other applications are also feasible. Background Art

[0002] Several electric migration separation techniques are used in the field of bioanalysis, particularly in the field of proteomics and metabolomics. Many techniques in these techniques are even more generally applied in the pharmaceutical and biopharmaceutical industries, particularly for protein analysis, particularly for the analysis of antibodies, charge variants or other protein forms. Especially, mass spectrometry has been applied as an important technology for identifying molecules (comprising large biomolecules such as proteins). The combination of electric migration separation technique and mass spectrometry may be challenging, particularly because the chemical substances (such as, surfactants) that are generally used in the electric migration separation technique may cause interference effects during measurement with mass spectrometry. Separating these chemical substances from samples can usually be realized via an extra separation dimension.

[0003] In WO2017153451 A1, a sample transfer device, an analysis system for analyzing a sample, a method for sample transfer, and a method for manufacturing a sample transfer device are disclosed. The sample transfer device includes: · at least one first block and at least one second block, wherein the first block includes at least one first port and at least one second port, wherein the second block includes at least one third port and at least one fourth port; · at least one slider, wherein the slider is located between the first block and the second block, wherein the slider is configured to slide from a first position to a second position, and vice versa; wherein, in both the first position and the second position, a first straight channel is formed between the first port and the third port, and a second straight channel is formed between the second port and the fourth port.

[0004] The publication by Schlecht J. et al., Analytical and Bioanalytical Chemistry (2018) 410: 6353-6359 describes the advantages, limitations and applications of two-dimensional capillary electrophoresis-mass spectrometry (CE-CE-MS) systems. In addition, an outlook for future developments is given.

[0005] In jooβk et ​​al., Analytical Biochemistry (2017) 409: 6057-6067, a heart-cut CZE-CZE-MS device is described, which has an implemented mechanical four-port valve interface, using a common ε-aminocaproic acid-based background electrolyte in the first dimension and acetic acid in the second dimension. Interference-free, high-precision mass data (deviation less than 1Da) for trastuzumab charge variants acting as a model mAb system were achieved. The mass accuracy obtained (parts per million range) was discussed for both measured and calculated masses. Deamidation was detected for intact model antibodies, and the relevant mass differences were significantly confirmed at the deglycosylation level. The CZE-CZE-MS device is expected to be applicable to a variety of antibody and electrolyte systems. Therefore, it has the potential to become a powerful tool for MS characterization of antibody variants separated in ESI-interfering electrolytes.

[0006] In Sánchez-Hernández L. et al., Electrophoresis, 2017, 38, 1044-1052, a CE-MS method for analyzing mAbs in SDS-complexed samples is proposed. In order to obtain narrow and strong peaks of SDS-treated antibodies, an intracapillary strategy based on co-injection of positively charged surfactants and methanol as organic solvents was developed. For samples containing 0.2% (v / v) SDS, up to 97% and 95% of the recovered MS peak intensity was obtained using hexadecyltrimethylammonium bromide or benzalkonium chloride, respectively. The successful removal of SDS is shown in neutrally coated capillaries, but also in capillaries with positively charged coatings, which apply the opposite polarity. The effectiveness of this intracapillary strategy has also been demonstrated for other proteins and antibodies dissolved in SDS solutions up to 10% v / v and in other SDS-containing matrices, including the sieving matrix used in the standard CE-SDS method and the gel buffer used in the SDS-PAGE method. The developed CE-MS method enables rapid and reproducible characterization of SDS-complexed antibodies.

[0007] Despite the advantages and progress achieved by the above-mentioned developments, some significant technical challenges remain. Thus, in general, known techniques for sample transfer often imply sealing challenges, such that leaks may occur. In addition, known systems and devices are often mechanically unstable, which often results in material wear and / or voltage drops. Furthermore, accurate transfer of samples from the first dimension to the second dimension while maintaining the high separation efficiency of the electrochemical separation technique is often challenging, particularly because of the small size of the utilized capillaries and / or the need for high electrical insulation that are often required.

[0008] Issues to be resolved

[0009] The object of the present invention is therefore to propose a valve, an analysis system for analyzing a sample, a method for transferring at least one fluid and a use of a valve which at least partially avoid the disadvantages of known devices and methods of this kind and which at least partially solve the above challenges. In particular, such devices and methods should be disclosed which allow accurate and reliable transfer of well-defined sample volumes, in particular small sample volumes, such as small sample volumes in the nanoliter range, and which can be used in particular for electromigration sample separation techniques. Summary of the invention

[0010] This problem is solved by a valve, an analysis system for analyzing a sample, a method for transferring at least one fluid and a use of a valve device having the features of the independent claims. Preferred embodiments are listed in the dependent claims, which can be realized individually or in any combination.

[0011] As used hereinafter, the terms "having", "including" or "comprising" or any grammatical variants thereof are used in a non-exclusive manner. Thus, these terms may refer both to the absence of additional features in the entity described in this context in addition to the features introduced by these terms, and to the presence of one or more additional features. For example, the expressions "A has B", "A includes B" and "A contains B" may refer both to the absence of additional elements in A in addition to B (i.e., A consists exclusively of B), and to the presence of one or more additional elements in the entity A in addition to B, such as element C, elements C and D or even additional elements.

[0012] In addition, it should be noted that when introducing corresponding features or elements, the terms "at least one", "one or more" or similar expressions indicating that the features or elements may appear one or more times will generally be used only once. In the following, in most cases, when referring to the corresponding features or elements, the expressions "at least one" or "one or more" will not be repeated, although the corresponding features or elements may exist once or more than once.

[0013] In addition, as used hereinafter, the terms "preferably", "more preferably", "especially", "more especially", "particularly", "more particularly" or similar terms are used in connection with optional features without limiting the possibility of substitution. Therefore, the features introduced by these terms are optional features and are not intended to limit the scope of the claims in any way. Those skilled in the art will recognize that the present invention can be formed by using alternative features. Similarly, the features introduced by "in an embodiment of the present invention" or similar expressions are intended to be optional features, without any limitation on alternative embodiments of the present invention, without any limitation on the scope of the present invention, and without any limitation on the possibility of combining the features introduced in this manner with other optional or non-optional features of the present invention.

[0014] The term "fluid" as used herein is a broad term, and has common and customary meanings for those of ordinary skill in the art, and is not limited to special or customized meanings. The term can particularly refer to but is not limited to any material, such as liquid or gas or a mixture thereof, which can flow and change its shape at a stable rate when subjected to the effect of a force that tends to change its shape. The terms "first fluid" and "second fluid" can be considered as terms only, and the named passages are numbered or sorted, without specifying an order and without excluding the possibility that there may be several types of the first fluid and the second fluid. In addition, other types of fluids may be present, such as one or more third fluids or the fourth fluid.

[0015] The term "sample" as further used herein may refer to any material or combination of materials used for analysis, testing or investigation. A sample may be something of limited quantity that is intended to resemble and represent a larger quantity. However, a sample may also include a complete specimen. A sample may be a solid sample, a liquid sample, or a gas sample, or a combination thereof. In particular, a sample may be a fluid sample, i.e., a sample that is completely or partially in a liquid and / or gaseous state. The quantity of a sample may be described by its volume, mass, or size. However, other dimensions are also possible. A sample may contain only one material or only one compound. Alternatively, a sample may include several materials or several pounds.

[0016] The term "analyte" generally refers to any element, component or compound that may be present in a sample and whose presence and / or concentration may be of interest. For example, at least one analyte may be selected from the group consisting of: proteins; peptides; metabolites, environmental contaminants, organic acids, in particular amino acids; pharmaceuticals; biomarkers, in particular cancer biomarkers; antibodies; impurities of pharmaceutical products, in particular biopharmaceuticals; variants of pharmaceutical products, in particular biopharmaceuticals. However, additionally or alternatively, other types of analytes may be used and / or any combination of analytes may be determined.

[0017] In a first aspect of the present invention, a valve for transferring at least one fluid is disclosed. As used herein, the term "valve" is a broad term, and for those of ordinary skill in the art, it has common and customary meanings, and is not limited to special or customized meanings. The term may particularly refer to, but is not limited to, any device that regulates, guides or controls the flow of a fluid, such as by opening, closing or partially blocking various channels. Therefore, a valve can be configured to partially or completely transfer or transfer a fluid from a first dimension or a first position to at least one other dimension or another position, such as a second dimension or a second position. However, other dimensions like the third dimension are also feasible. Therefore, the valve may also be referred to as a fluid transfer device or a sample transfer device.

[0018] "Dimension" can be or can include any volume, such as a container or channel, configured to at least partially receive a fluid. However, other embodiments are also feasible. The first dimension and the other dimension can be separate dimensions, so that a fluid or a portion of a fluid can be transferred from the first dimension to the other dimension only through a barrier or space therebetween, or vice versa. The valve can be configured to transfer a portion of the fluid or transfer a specific component of the fluid that a user may be interested in, such as one or more of the analytes of the fluid.

[0019] The valve includes at least one stator. The stator includes a plurality of ports. The ports include a plurality of groups of ports. The plurality of groups of ports include a first group of at least two first ports, a second group of at least two second ports, and a third group of at least two third ports. In addition, the valve includes at least one rotor. The rotor includes a plurality of channels. The channels include at least one first channel and at least one second channel. In addition, the valve includes at least one actuator. The actuator is operably connectable to the rotor. The actuator is configured to rotate the rotor into at least one loading orientation. In the loading orientation, one or both of the following conditions exist:

[0020] a) the first channel is connected to the first ports so that the first fluid can be transferred into the first channel via at least one of the first ports;

[0021] b) The second channel is connected to the second ports such that the second fluid can be transferred into the second channel via at least one of the second ports.

[0022] The actuator is further configured to rotate the rotor into at least one first injection orientation and at least one second injection orientation. In the first injection orientation, the first channel is connected to the third port, and the first fluid can be transferred from the first channel to at least one of the third ports. In the second injection orientation, the second channel is connected to the third port, and the second fluid can be transferred from the second channel to at least one of the third ports. Optionally, in case a), the first fluid can also be transferred back to one of the first ports. In case b), optionally, the second fluid can also be transferred back to one of the second ports.

[0023] The term "stator" as used herein is a broad term and has an ordinary and customary meaning to a person of ordinary skill in the art and is not limited to a special or customary meaning. The term may particularly refer to, but is not limited to, any component of a machine that remains at least substantially fixed relative to a rotating part of the machine. The stator may have a cylindrical shape. However, other shapes are also possible. The stator may be attached to the actuator via screws, and the rotor may be located between the stator and the actuator, the rotor being described in further detail below.

[0024] As mentioned above, the stator includes a plurality of ports. As used herein, the term "port" is a broad term, and for those of ordinary skill in the art, it has a common and customary meaning, and is not limited to a special or customized meaning. The term may particularly refer to, but is not limited to, any unit that can be configured to connect two or more elements to each other so that a fluid medium or a solid medium can be transferred from one element to another. In particular, a port can be a part of a channel with at least one opening, which allows fluid to enter or leave the channel and / or allows a fluid fluid to be connected to the channel. Exemplarily, a port can be connected to a device and / or a blood vessel via a capillary. However, other embodiments are also feasible. The port can be a tight port in particular, which is configured to prevent fluid leakage at least to a great extent. Therefore, the port can have a low dead volume. The capillary can be connected in particular by gluing, bonding or welding or by using a component of a port fitting and a threadable fitting. The term "multiple ports" refers to the presence of more than one port. In particular, the stator can include a total of six ports. More particularly, the stator can include a total of eight ports. However, smaller or higher number of ports are also feasible.

[0025] The terms "first port" and "second port" may be considered as terms only, without numbering or ordering the named elements, without specifying an order, and without including the possibility that there may be several kinds of first ports and second ports. In addition, there may be additional ports, such as one or more third ports, which will be described in further detail below.

[0026] The term "group of ports" may refer to two or more ports that share at least one common feature. In particular, the ports in a single port group may be connected, in particular fluidically connected, to a single external additional device, such as an analytical device, a sample separation device, or a fluid support, such as a syringe. Thus, one port in the port group may serve as an inlet, and another port in the same port group may serve as an outlet. The inlet may be configured to supply a fluid (such as a sample) to a channel of a rotor, and the outlet may be configured to direct the fluid away from the channel. Therefore, the ports of a single port group may be configured to establish a fluid circuit between an external additional device and one of the channels of a rotor. These channels will be described in further detail below.

[0027] The terms "first group" and "second group" may be considered as terms only, without numbering or sorting the named groups, without specifying an order, and without excluding the possibility that there may be several kinds of first and second groups. In addition, there may be additional groups, such as one or more third groups. In particular, the plurality of ports may further include at least one fourth group of at least two fourth ports. In addition, the channel may include at least one fourth channel.

[0028] The term "rotor" as used herein is a broad term and has an ordinary and customary meaning to a person of ordinary skill in the art and is not limited to a special or customary meaning. The term may particularly refer to, but is not limited to, any rotating part of a machine. The rotor may be capable of rotating around the axis of the rotor. By rotating, the rotor may change its orientation. The rotation may be caused by an interaction between the windings and the magnetic field, which interaction may produce a torque around the axis of the rotor. Therefore, the term "rotation" may refer to the rotation of the rotor around the axis of the rotor center point. In addition, the term "rotation" may refer to a change in the orientation of the rotor.

[0029] The rotor may have a cylindrical reinforced shape. In particular, the rotor may have a cylindrical reinforced shape with a small thickness. The rotor may have a thickness of at least 1.5 mm, preferably at least 2 mm, more preferably at least 2.5 mm, most preferably at least 3 mm. However, other dimensions are also feasible.

[0030] The rotor may include at least one polymer material; a ceramic material; glass; at least one non-conductive material.

[0031] In particular, the channel is formed as a recess, such as a receptacle or notch, in the surface of the rotor. Thus, the channel may be an "open channel". As further used herein, the term "open channel" may generally refer to a groove or a groove cut into a surface of a solid material, in particular a smooth surface of a solid material. The open channel may be through-going, such that the open channel may pass all the way through the surface of the solid material and such that the ends of the open channel may be accessible. Alternatively, the open channel may stop, such that one or both ends may end before the open channel meets the edge of the surface.

[0032] The groove may be at least partially covered by at least one covering element. The term "covering element" may generally refer to any element having a surface configured to be attachable to a further surface of another element. Therefore, the shape of the surface of the covering element and the shape of the further surface of the further element may complement each other. Exemplarily, the surface of the covering element and the further surface of the further element may be flat surfaces, so that a tight connection between the surface and the further surface may be formable. The covering element may in particular be made of an optically transparent material, such as glass. However, other materials are also feasible.

[0033] The term "channel" as used herein is a broad term and has common and special meanings for those of ordinary skill in the art, and is not limited to special or customized meanings. The term may particularly refer to, but is not limited to, any element that may have an elongated shape and may provide a free volume or inner cavity and allow a fluid medium to flow through. Therefore, the channel may be configured to receive a solid or fluid medium and / or provide a transfer of a medium from one end of the channel to the other end of the channel. The channel may preferably be a tight channel so that leakage of the medium may be prevented at least to a great extent.

[0034] The terms "first channel" and "second channel" may be considered as terms only, not as numbering or ordering the named channels, not as specifying an order, and not excluding the possibility that there may be several kinds of first channels and second channels. In addition, additional channels may exist. In particular, the channels may further include at least one third channel. In the loading orientation (which will be described in further detail below), the third channel may be connected to the third port.

[0035] The term "multiple channels" refers to the presence of more than one channel. In particular, the rotor may comprise a total of two or three channels. More particularly, the rotor may comprise a total of four channels. However, a smaller or higher number of channels is also feasible.

[0036] Each channel can be designed so that the channel is connected to the corresponding port group at this time, and the channel and the port group can form a loop. Therefore, the fluid can be transferred to the channel from at least one port of the port group, and returned from the channel to at least one other port of the port group. Therefore, as described above, a port in the port group can serve as an inlet, and another port in the same port group can serve as an outlet. The inlet can be configured to supply fluid (such as a sample) to the channel of the rotor, and the outlet can be configured to guide the fluid away from the channel. Each channel may include a first end and a second end. In a loading orientation or in one of the injection orientations, a port in the port group can be located at (e.g., fluid is connected) at the first end of a channel, and another port in the same group of ports can be located at the second end of the same channel.

[0037] The channels can be specifically configured to connect a group of ports to each other. Thus, a first channel can be configured to connect two first ports to each other in the loading orientation and to connect two third ports to each other in the first injection orientation. Furthermore, a second channel can be configured to connect two second ports to each other in the loading orientation and to connect two third ports to each other in the second injection orientation.

[0038] The channel may be at least partially located on a virtual circle. The virtual circle may be located on at least one surface of the rotor. As used herein, the term "virtual circle" generally refers to a line defined by its distance from a center point. In addition to this property, the circle does not have to be structurally distinguished from the remaining surfaces of the rotor. In particular, the center point of the virtual circle may correspond to the axis of rotation of the rotor. The channel may have two ends, respectively. The ends may be located on virtual circles, respectively. In particular, the channel may correspond to a circle segment of a virtual circle, respectively. In particular, the channel may have a shape selected from the group consisting of: a straight shape, a semicircular shape, a semi-elliptical shape, a U-shaped shape. However, other shapes are also feasible. Therefore, the channel may have a shape selected from the group consisting of: a straight shape, a semicircular shape, a semi-elliptical shape, a U-shaped shape.

[0039] The first channel may have a first distance to the axis of rotation of the rotor, and the second channel may have a second distance to the axis of rotation. The third channel may have a third distance to the axis of rotation. In addition, the rotor may have a fourth channel, which will be described in further detail below. The fourth channel may have a fourth distance to the axis of rotation. The first distance and the second distance may be substantially equal. In addition, the first distance, the second distance and the third distance may be substantially equal. In addition, the first distance, the second distance, the third distance and the fourth distance may be substantially equal. The term "substantially equal" may refer to the possibility of a line of sight variation between different distances. Thus, one of the distances may show a maximum deviation of 10% from one of the other distances, preferably a maximum deviation of 5% from one of the other distances, more preferably a maximum deviation of 2% from one of the other distances.

[0040] As described above, the first channel comprises at least one first channel end, and the second channel comprises at least one second channel end. The first channel end and the second channel end may face each other. The distance between the first channel end and the second channel end may be at least 1 mm, preferably at least 2 mm, more preferably at least 3 mm. Due to the high distance between the channels and therefore between the ports, a higher separation voltage can be applied. At least 25 kV can now be applied. By applying the known valve, only a maximum value of 15 kV can be achieved without sparks between the ports. This mainly speeds up the overall analysis. The greater thickness of the rotor compared to the rotor of the known valve can also contribute to the possibility of applying higher voltages.

[0041] The volume of at least one of the channels can be 1nl to 500nl, preferably 5nl to 100nl, preferably 10nl to 40nl, and most preferably 20nl. In particular, the first channel can have a first volume and the second channel can have a second volume. In addition, the third channel can have a third volume. In addition, the fourth channel can have a fourth volume. The first volume and the second volume can be identical. In particular, one or both of the first volume, the second volume, and the third and fourth volumes can be identical. The term "identical" can include slight variations between different volumes. Therefore, one of the volumes can show a maximum deviation of 10% from one of the other volumes, preferably a maximum deviation of 5% from one of the other volumes, and more preferably a maximum deviation of 2% from one of the other volumes. Alternatively, the first volume and the second volume can be different from each other. In particular, one or both of the first volume and the second volume and the third and fourth volumes can be different from each other.

[0042] The channel can be a microfluidic channel. As further used herein, the term "microfluidic channel" can refer to a channel size that is small, typically sub-millimeter scale. The channel can be micro-fabricated. Exemplarily, the channel can have a circular cross-section, an elliptical cross-section, or a trapezoidal cross-section at least in part, with a diameter of 5 μm to 500 μm, preferably 20 μm to 100 μm. In addition, the channel can have a rectangular cross-section at least in part, with a width of 20 μm to 500 μm, preferably 50 μm to 200 μm, and more preferably 100 μm, and a depth of 5 μm to 100 μm, preferably 10 μm to 50 μm, and more preferably 100 μm. However, other embodiments are also feasible. In addition, one or more of the channels can have a length of 0.5 mm to 5 mm, preferably 0.8 mm to 2 mm, more preferably 0.9 mm to 1 mm, and most preferably 0.95 mm.

[0043] The term "actuator" as used herein is a broad term and has a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term may particularly refer to, but is not limited to, any element configured to move or control a mechanism or system. The actuator may be operated by an energy source (typically an electric current or mechanical pressure) and may convert energy into motion. The actuator may be selected from the group consisting of: a mechanical actuator, an electromagnetic actuator, a pneumatic actuator, a hydraulic actuator. However, other types of actuators may also be applied. The term "operably connected" as further used herein may refer to a property of an actuator and a rotor, that is, being able to be connected in such a way that the rotor realizes its function, such as rotation, by being operated or triggered by the actuator. Therefore, an electrical connection may exist between the actuator and the rotor. The actuator may be configured to rotate the rotor from a loading orientation to a first injection orientation, and from a first injection orientation to a second injection orientation, and vice versa. Furthermore, the actuator may be configured to rotate the rotor to a third injection orientation, in particular from the second injection orientation to the third injection orientation.

[0044] The term "orientation" as used herein is a broad term and has an ordinary and customary meaning to a person of ordinary skill in the art and is not limited to a special or customary meaning. The term may particularly refer to, but is not limited to, the arrangement of a point of an element relative to an axis of the element that is positioned transversely to the axis of rotation of the element. Although the distance between a point and the axis of rotation of the element may remain the same during a change in orientation, such as by rotating the element, the angle of the point relative to the axis may change during the change in orientation. Thus, the rotor may assume different orientations, such as a loading orientation, a first injection orientation, and a second injection orientation, by rotating about the axis of the rotor.

[0045] The term "loading orientation" as used herein is a broad term and has a common and customary meaning for a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term may particularly refer to, but is not limited to, any orientation of the rotor in which one or more of the channels, particularly one or more of the first channel, the second channel, and the fourth channel, are filled with a fluid. In particular, the first channel may be filled with a first fluid, and the second channel may be filled with a second fluid. In addition, the fourth channel may be filled with a fourth fluid. As described above, the actuator is configured to rotate the rotor into at least one loading orientation. Thus, in particular, the actuator may be configured to rotate the rotor into a single loading orientation. In a single loading orientation, the first channel may be connected to the first port so that the first fluid may be transferred to the first channel via at least one of the first ports, and at the same time, the second channel may be connected to the second port so that the second fluid may be transferred to the second channel via at least one of the second ports. In addition, at the same time, the fourth channel may be connected to the fourth port so that the fourth fluid may be transferred to the fourth channel via at least one of the fourth ports. Thus, the loading of the first channel and the second channel and optionally also the fourth channel may be performed simultaneously, for example, at the same time. However, additionally or alternatively, the actuator may be configured to rotate the rotor into a plurality of loading orientations. Thus, illustratively, in a first loading orientation, the first channel may be connected to the first port so that the first fluid may be transferred into the first channel via at least one of the first ports. Furthermore, in a second loading orientation different from the first loading orientation, the second channel may be connected to the second port so that the second fluid may be transferred into the second channel via at least one of the second ports. Furthermore, in a fourth loading orientation different from the first loading orientation and the second loading orientation, the fourth channel may be connected to the fourth port so that the fourth fluid may be transferred into the fourth channel via at least one of the fourth ports. Thus, the loading of the first channel, the second channel and the optional fourth channel may be performed one after the other, for example, sequentially.

[0046] The term "fluid is transferable" may generally refer to the active or passive transport of any fluid from one location to another, or vice versa. Thus, the term "active transport" generally means that the transport is supported by an external force and / or drive device, such as a pump or valve for directional transport of materials. Thus, the term "active transport" may also refer to the defined manipulation of a fluid. The term "passive transport" may refer to transport without external actuation, and illustratively includes transport by capillary forces.

[0047] The term "channel connected to ports" may generally refer to an arrangement of one of the channels to a port group such that transfer of fluid from one of the port groups to another port group via the channel or vice versa is provided.

[0048] The term "injection orientation" as used herein is a broad term and has a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or customary meaning. The term may particularly refer to, but is not limited to, any orientation of the rotor in which one of the channels can be connected to the third port and the fluid can be transferred from the channel to one of the third ports. The terms "first injection orientation" and "second injection orientation" may be considered to be merely terms, rather than numbering or sorting the named injection orientations, not specifying an order, and not excluding the possibility that there may be several kinds of first injection orientations and second injection orientations. In addition, there may be additional injection orientations, such as one or more third injection orientations. The actuator may be configured to rotate the rotor into a plurality of injection orientations. Thus, illustratively, in the first injection orientation, the first channel may be connected to the third port so that the first fluid can be transferred from the first channel to one of the third ports. Furthermore, in the second injection orientation, the second channel may be connected to the third port so that the second fluid can be transferred from the second channel to one of the third ports. Furthermore, in the third injection orientation, the fourth channel may be connected to the third port so that the fourth fluid can be transferred from the fourth channel to one of the third ports. Thus, injecting the fluid into one of the third ports may be performed one after another, for example, sequentially.

[0049] As described above, the plurality of ports may further include at least one fourth group of at least two fourth ports. In addition, the channel may include at least one fourth channel. In the loading orientation, the following may occur:

[0050] c) The fourth channel is connected to the fourth port so that the fourth fluid can be transferred into the fourth channel.

[0051] Optionally, in case c), the fourth fluid may be transferred back into the fourth port. In addition, the actuator may be configured to rotate the rotor into at least one third injection orientation. In the third injection orientation, the fourth fluid may be transferred from the fourth channel into at least one of the third ports.

[0052] One or more of the port groups may be respectively connected to at least one pump for providing a fluid, in particular at least one syringe pump or any other liquid delivery system. In particular, the second port and / or the fourth port may be respectively connected to a pump for providing a fluid, in particular a syringe pump. The second channel and the fourth channel may be positioned on opposite sides of the rotor relative to the axis of rotation of the rotor. However, other configurations are also possible.

[0053] Thus, channels that can be used for CE (SDS) and CZE-MS can be positioned on opposite sides. Thus, the ports can be more independent compared to ports of known valves. Thus, small amounts of fluid leakage between the stator and rotor (such as SDS) can have limited impact on CZE-MS separation. Thus, higher analytical stability is feasible.

[0054] The rotor may also include at least one cavity configured to receive excess fluid. The term "cavity" may generally refer to any void volume within a solid material surface, such as a rotor surface. The cavity may have a size in the sub-millimeter range and may therefore be microfabricated. In addition, the cavity may have at least one cross-section selected from the group consisting of: a circular cross-section, an elliptical cross-section, a polygonal cross-section, in particular a rectangular cross-section. In particular, the cavity may be embodied as a channel.

[0055] In another aspect of the invention, an analytical system for analyzing a sample is disclosed.

[0056] As further used herein, the term "system" refers to a group of at least two elements, which can interact to achieve at least one common function. The at least two components can be processed independently, or can be coupled, connected or integrated to form a common component. Therefore, an "analysis system" generally refers to a group of at least two elements or components that can interact, so as to perform at least one sample transfer and / or at least one analysis detection, particularly at least one analysis detection of a sample analyte. An analysis system may also be generally referred to as an analysis kit, a sensor system or a measurement system.

[0057] The analysis system comprises a valve as described above or as will be described further below. However, it should be noted that other embodiments are also possible. Furthermore, the analysis system further comprises at least one analysis device fluidically connectable to the two third ports.

[0058] The term "analyzer" generally refers to any device configured to perform at least one analytical measurement. The analytical device may preferably be an electronic device, which can be processed independently of the sample transfer device. The analytical device may be adapted to interact with the sample transfer device in order to obtain at least one information of an analyte of the sample. In particular, the analytical device may be adapted to detect at least one signal generated by the analyte, as will be described in further detail below. Therefore, the analytical device may include at least one electronic evaluation device to derive at least one information of the analyte from the at least one signal. Therefore, the analytical device may include at least one evaluation unit, which includes at least one data processing device, such as a microcontroller.

[0059] In addition, the analytical system may include at least one sample separation device that can be fluidically connected to the first port. The term "separation" can generally refer to any process that eliminates a specific component of a material or sample, or can also refer to any process that removes at least a portion of a material or sample from its original residence. Therefore, the removed portion of the material or sample and the remaining portion of the material or sample can have different chemical compositions, respectively. The sample separation device can be selected from the group consisting of: an electromigration device, in particular capillary zone electrophoresis (CZE), in particular capillary sieving electrophoresis (CSE), in particular capillary sieving electrophoresis (CSE) of proteins complexed with a surfactant (such as sodium dodecyl sulfate), in particular capillary isoelectric focusing (CIEF), in particular imaging CIEF (ICIEF); a chromatographic device, in particular a liquid chromatography device (LC), in particular a size exclusion chromatography (SEC) device, in particular an ion chromatography (IC) device, preferably a capillary electrophoresis device, as well as a reversed phase liquid chromatography and a hydrophilic liquid interaction chromatography (HILIC).

[0060] The analytical device can be selected from the group consisting of: a mass spectrometer coupled online to the liquid phase separation device, preferably atmospheric pressure ionization (API)-MS, more preferably electrospray ionization, atmospheric pressure chemical ionization or atmospheric pressure photoionization mass spectrometer. The analytical system can further include at least one characterization unit. The characterization unit can be located between the sample separation device and one of the first ports. In addition, the characterization unit can be configured to characterize at least one property of the first fluid. In particular, the characterization unit can be an optical or conductivity detection unit.

[0061] In another aspect of the invention, a method for transferring at least one fluid is disclosed. As used herein, the term "transferring at least one fluid" is a broad term and has an ordinary and customary meaning to one of ordinary skill in the art and is not limited to a special or customary meaning. The term may particularly refer to, but is not limited to, any process of transporting a fluid from one location to another or vice versa, such as by active or passive transport as described above.

[0062] The method for transferring at least one fluid comprises the method steps as given in the independent claim and listed below. The method steps can be performed in a given order. However, other orders of the method steps are also feasible. In addition, one or more method steps can be performed in parallel and / or in a time-overlapping manner. In addition, one or more method steps can be repeatedly performed. In addition, there can be additional method steps that are not listed.

[0063] The method uses a valve as described above or further described below. However, it should be noted that other embodiments are also possible. The method comprises the following steps:

[0064] I. While the rotor is in the loading orientation, perform one or both of the following steps:

[0065] I.1 supplying a first fluid into the first channel while the first channel is connected to the first port;

[0066] I.2 supplying a second fluid into the second channel while the second channel is connected to the second port;

[0067] II. transferring the first fluid to one of the third ports by rotating the rotor into the first injection orientation, in particular from the loading orientation to the first injection orientation;

[0068] III. Transferring the second fluid to one of the third ports by rotating the rotor into a second injection orientation, in particular from the first injection orientation to the second injection orientation.

[0069] As further used herein, the term "supply" as used herein is a broad term and has an ordinary and customary meaning to one of ordinary skill in the art and is not limited to a special or customary meaning. The term may particularly refer to, but is not limited to, any process of adding or loading a material or sample to any free volume. Thus, the free volume may be in fluid connection with the material or sample. Thus, as described above or as will be further described below, the material or sample may be transferred to the free volume by active or passive transport.

[0070] In particular, the plurality of groups of ports may include a fourth group of at least two fourth ports. The channels may also include at least one fourth channel, and the method may further include the following steps:

[0071] I.3 supplying a fourth fluid into the fourth channel while the rotor is in the loading orientation and the fourth channel is connected to the fourth port;

[0072] IV. Diverting the fourth fluid to one of the third ports by rotating the rotor to a third injection orientation, in particular from the second injection orientation to the third injection orientation.

[0073] In a further aspect of the invention, the use of a valve as described above or as further described below is described for at least one purpose selected from the group consisting of: mass spectrometric detection of protein analysis and proteomics (such as protein charge variants or protein forms), and metabolite analysis and metabolomics; electrically driven separation techniques and connection of chromatographic separations to a mass spectrometer.

[0074] The proposed sample transfer device, the proposed analysis system for analyzing a sample, the proposed method for sample transfer and the proposed method for manufacturing a sample transfer device offer numerous advantages over known devices and methods.

[0075] To implement the decomplexation strategy, typically, the peak of interest must be shifted from the CE (SDS) dimension between methanol and the cationic surfactant in the CZE-MS dimension. Successful decomplexation of SDS-protein complexes often requires ensuring simultaneous localization in both dimensions. Correct localization is often a critical factor for a successful analysis and is often challenging due to imprecise localization detection.

[0076] Due to the high creep tendency of the SDS between stator and rotor, leaks often result when the valve is not tight or after a period of use. Even a small leak may connect the actual independent CE (SDS) and CZE-MS dimensions, so current instability and total failure of the analysis may be the result. Therefore, a larger distance between the separation dimensions will be beneficial to keep the circuits independent and stable during the analysis. In common valves, each channel can have a different volume. Therefore, before starting the adjustment for the second analysis, the previous analysis usually has to be completed and the valve must be switched back.

[0077] With the new valve, it is possible to more precisely position decomplexing plugs, such as methanol and / or cationic surfactants, and apply higher separation voltages. Due to the new geometry, higher robustness against SDS leakage is also possible, and simultaneous adjustment of CE(SDS) dimensions can save additional time. Therefore, CE(SDS)-CZE-MS analysis using the new valve can be faster, more reproducible and more robust. By combining CE(SDS) and online SDS-protein decomplexation strategies through the valve, it is feasible to obtain online mass information from CE(SDS) separated peaks.

[0078] The valve can have six ports, in particular eight ports. Compared with the channels of known valves, channels, in particular loops, can be arranged farther away from each other. Although known valves generally have channels with a distance of 0.85 mm, the distance between the channels of the valve according to the present invention can be 3.14 mm, and the distance between the channels of known valves can be 0.85 mm. The channel of the valve according to the present invention can have a volume of 40 nl, and the channel of the known valve can have a volume of 4nl to 20 nl. These channels may now all have the same volume. Therefore, there may be 4-fold symmetry. Due to the 4-fold geometry, the CE (SDS) dimension can be prepared (adjusted) for the next analysis, while the separation occurs in the CZE-MS dimension. This is a very time-saving factor, because the adjustment takes about 1 hour, and the analysis in CZE takes about 30 minutes. Therefore, 30 minutes of time can be saved.

[0079] Furthermore, the rotor can be thicker than before (before: 1 mm; now: 3 mm). Different circuit volumes may be available here, such as 10 nl, 20 nl or 40 nl. The valve can now have a universal actuator. Thus, the rotor can be switched in both directions to each programmed orientation. The rotor can in particular be obtained in different polymer materials.

[0080] The ethanol and cationic surfactant plugs can now have their own ports and can be positioned more precisely by diverting the filled channel to the third port, particularly to the CZE-MS dimension and particularly by applying pressure to transfer a defined volume. Other channels and ports can be used for CE (SDS) and CZE-MS analysis. Here, a higher reproducibility of plug positioning and decomplexation may be feasible. This may lead to a higher analysis success rate.

[0081] Utilize new valve, perhaps be possible to obtain mass spectrum from separated protein via CE (SDS).The location of peak of interest in CE (SDS) and the location of methanol and cationic surfactant can be done simultaneously.The speed of CE (SDS) peak can be determined by external UV detector.On the contrary, by utilizing known valve, the speed of methanol and cationic surfactant can be determined by external C4D detector.In addition, when CE (SDS) is not the first separation dimension, the proposed valve can be used for multi-heart cut (heart cut) analysis.

[0082] Compared to known valve rotors, the valve rotor according to the invention can have a greater number of channels. The channels can be applied to transfer solvents. However, the channels can also be applied to transfer samples. In particular, multiple fractions can be applied.

[0083] To summarize and without excluding further possible embodiments, the following embodiments may be envisaged:

[0084] Embodiment 1: A valve for transferring at least one fluid, comprising:

[0085] at least one stator, wherein the stator comprises a plurality of ports, the ports comprising a plurality of groups of ports, the plurality of groups of ports comprising a first group of at least two first ports, a second group of at least two second ports, and a third group of at least two third ports;

[0086] at least one rotor, wherein the rotor comprises a plurality of channels, the channels comprising at least one first channel and at least one second channel; and

[0087] at least one actuator, wherein the actuator is operably connectable to the rotor;

[0088] wherein the actuator is configured to rotate the rotor into at least one loading orientation, wherein in the loading orientation, one or both of the following conditions exist:

[0089] a) the first channel is connected to the first ports so that the first fluid can be transferred into the first channel via at least one of the first ports;

[0090] b) the second channel is connected to the second ports so that the second fluid can be transferred into the second channel via at least one of the second ports;

[0091] wherein the actuator is further configured to rotate the rotor into at least one first injection orientation, wherein in the first injection orientation, the first channel is connected to the third port and the first fluid is transferable from the first channel to at least one of the third ports, and wherein in the second injection orientation, the second channel is connected to the third port and the second fluid is transferable from the second channel to at least one of the third ports.

[0092] Embodiment 2: A valve according to the aforementioned embodiment, wherein each channel is designed so that when the channel is connected to a corresponding group of ports, the channel and the group of ports form a loop, wherein fluid can be transferred from at least one port of the group of ports into the channel and returned from the channel to at least another port in the group of ports.

[0093] Embodiment 3: The valve according to any of the preceding embodiments, wherein the plurality of ports further comprises at least one fourth group of at least two fourth ports, wherein the channel further comprises at least one fourth channel.

[0094] Embodiment 4: A valve according to the preceding embodiment, wherein in the loading orientation the following conditions exist:

[0095] c) The fourth channel is connected to the fourth port so that the fourth fluid can be transferred into the fourth channel.

[0096] Embodiment 5: The valve according to any of the two preceding embodiments, wherein the actuator is further configured to rotate the rotor into at least one third injection orientation, wherein in the third injection orientation, a fourth fluid is divertible from the fourth channel into at least one of the third ports.

[0097] Embodiment 6: The valve according to any one of the three preceding embodiments, wherein the second port and the fourth port are respectively connectable to at least one pump for providing fluid, in particular, to at least one syringe pump or any other liquid delivery system.

[0098] Embodiment 7: The valve according to the previous embodiment, wherein the second channel and the fourth channel are positioned on opposite sides of the rotor relative to the rotation axis of the rotor.

[0099] Embodiment 8: The valve according to any of the preceding embodiments, wherein the channel further comprises at least one third channel, wherein in the loading orientation the third channel is connected to the third port.

[0100] Embodiment 9: The valve according to any of the preceding embodiments, wherein the channel is located at least partially on a virtual circle, wherein a center point of the virtual circle corresponds to the rotation axis of the rotor, wherein the channel each has two ends.

[0101] Embodiment 10: A valve according to the preceding embodiment, wherein the end portions are respectively located on virtual circles.

[0102] Embodiment 11: The valve according to the preceding embodiment, wherein the channels respectively correspond to segments of a virtual circle.

[0103] Embodiment 12: The valve according to any one of the two preceding embodiments, wherein the channels respectively have shapes selected from the group consisting of: a straight shape, a semicircular shape, a semi-elliptical shape, a U-shape.

[0104] Embodiment 13: A valve according to any of the preceding embodiments, wherein at least one of the channels has a volume of 1 nl to 500 nl, preferably 5 nl to 100 nl, preferably 10 nl to 40 nl, most preferably 20 nl.

[0105] Embodiment 14: The valve according to any of the preceding embodiments, wherein the first channel has a first volume, wherein the second channel has a second volume, wherein the first volume and the second volume are equal or wherein the first volume and the second volume are different from each other.

[0106] Embodiment 15: A valve according to any of the preceding embodiments, wherein the channel is a microfluidic channel.

[0107] Embodiment 16: A valve according to any of the preceding embodiments, wherein the length of one or more of the channels is 0.5 mm to 5 mm, preferably 0.8 mm to 2 mm, more preferably 0.9 mm to 1 mm, and most preferably 0.95 mm.

[0108] Embodiment 17: A valve according to any of the preceding embodiments, wherein one or more of the channels have a substantially straight shape.

[0109] Embodiment 18: The valve of any of the preceding embodiments, wherein the first passage has a first distance to the rotation axis of the rotor, wherein the second passage has a second distance to the rotation axis, wherein the first distance and the second distance are substantially equal.

[0110] Embodiment 19: A valve according to any one of the preceding embodiments, wherein the first channel includes at least one first channel end, wherein the second channel includes at least one second channel end, wherein the first channel end and the second channel end face each other, wherein the distance between the first channel end and the second channel end is at least 1 mm, preferably at least 2 mm, and more preferably at least 3 mm.

[0111] Embodiment 20: A valve according to any of the preceding embodiments, wherein the thickness of the rotor is at least 1.5 mm, preferably at least 2 mm, more preferably at least 2.5 mm, and most preferably at least 3 mm.

[0112] Embodiment 21: A valve according to any of the preceding embodiments, wherein the channel is formed as a groove in the rotor surface.

[0113] Embodiment 22: The valve according to the preceding embodiment, wherein the recess is at least partially covered by at least one covering element.

[0114] Embodiment 23: A valve according to any of the preceding embodiments, wherein the rotor comprises at least one polymer material; a ceramic material; glass; at least one non-conductive material.

[0115] Embodiment 24: The valve of any of the preceding embodiments, wherein the actuator is configured to rotate the rotor from the loading orientation into the first injection orientation, and from the first injection orientation into the second injection orientation, and vice versa.

[0116] Embodiment 25: A valve according to any of the preceding embodiments, wherein the actuator is selected from the group consisting of: a motor, in particular an electric motor; a mechanical actuator; an electromagnetic actuator; a pneumatic actuator; a hydraulic actuator.

[0117] Embodiment 26: An analysis system for analyzing a sample, wherein the analysis system comprises the valve according to any one of the preceding embodiments, wherein the analysis system further comprises at least one analysis device fluidically connectable to the two third ports.

[0118] Embodiment 27: The analysis system according to any one of the two preceding embodiments, wherein the analysis system further comprises at least one sample separation device fluidically connectable to the first port.

[0119] Embodiment 28: An analytical system according to the preceding embodiments, wherein the sample separation device is selected from the group consisting of: an electromigration device, in particular capillary zone electrophoresis (CZE), in particular capillary sieving electrophoresis (CSE), in particular capillary sieving electrophoresis (CSE) of proteins complexed with a surfactant (such as sodium dodecyl sulfate), in particular capillary isoelectric focusing (CIEF), in particular imaging CIEF (iCIEF); a chromatography device, in particular a liquid chromatography device (LC), in particular a size exclusion chromatography (SEC) device, in particular an ion chromatography (IC) device, preferably a capillary electrophoresis device, as well as reversed phase liquid chromatography and hydrophilic liquid interaction chromatography (HILIC).

[0120] Embodiment 29: An analytical system according to the aforementioned three embodiments, wherein the analytical device is selected from the group consisting of: a mass spectrometer coupled online to a liquid phase separation device, preferably an atmospheric pressure ionization (APl)-MS, more preferably an electrospray ionization, atmospheric pressure chemical ionization or atmospheric pressure photoionization mass spectrometer.

[0121] Embodiment 30: An analysis system according to any one of the four preceding embodiments, wherein the analysis system further comprises at least one characterization unit, wherein the characterization unit is located between the sample separation device and one of the first ports, wherein the characterization unit is configured to characterize at least one property of the first fluid.

[0122] Embodiment 31: The analytical system according to the preceding embodiment, wherein the characterization unit is an optical or conductivity detection unit.

[0123] Embodiment 32: A method for transferring at least one fluid, the method using a valve according to any one of the preceding embodiments involving a valve, the method comprising the following steps:

[0124] I. While the rotor is in the loading orientation, perform one or both of the following steps:

[0125] I.1 supplying a first fluid into the first channel while the first channel is connected to the first port;

[0126] I.2 supplying a second fluid into the second channel while the second channel is connected to the second port;

[0127] II. transferring the first fluid to one of the third ports by rotating the rotor into the first injection orientation, in particular from the loading orientation to the first injection orientation;

[0128] III. Transferring the second fluid to one of the third ports by rotating the rotor into a second injection orientation, in particular from the first injection orientation to the second injection orientation.

[0129] Embodiment 33: The method according to the previous embodiment, wherein the port further comprises at least two fourth ports, wherein the channel further comprises at least one fourth channel, wherein the method further comprises the following steps:

[0130] I.3 supplying a fourth fluid into the fourth channel while the rotor is in the loading orientation and while the fourth channel is connected to the fourth port;

[0131] IV. Diverting the fourth fluid to one of the third ports by rotating the rotor into a third injection orientation, in particular from the second injection orientation to the third injection orientation.

[0132] Embodiment 34: Use of a valve according to any of the preceding embodiments involving valves for a purpose selected from the group consisting of: mass spectrometric detection of protein analysis and proteomics, such as protein charge variants or protein forms, and metabolite analysis and metabolomics; electrically driven separation technology and connection of chromatographic separation to a mass spectrometer. BRIEF DESCRIPTION OF THE DRAWINGS

[0133] Further optional features and embodiments will be disclosed in more detail in the subsequent description of embodiments, preferably in conjunction with the dependent claims. Wherein, as will be appreciated by those skilled in the art, the corresponding optional features can be implemented in an independent manner and in any arbitrary feasible combination. The scope of the present invention is not limited by the preferred embodiments. Embodiments are schematically depicted in the accompanying drawings. Wherein, the same reference numerals in these figures refer to the same or functionally equivalent elements.

[0134] In the figure:

[0135] Figure 1 An exemplary embodiment of a valve according to the invention is shown in an exploded view;

[0136] Figures 2A to 2B In perspective ( Figure 2A ) and top view ( Figure 2B ) shows an exemplary embodiment of a valve according to the present invention;

[0137] Figures 3A to 3C An exemplary embodiment of a rotor of a valve according to the invention is shown;

[0138] Figures 4A to 4D A further exemplary embodiment of a rotor of a valve according to the invention is shown;

[0139] Figures 5A to 5B An exemplary embodiment of an analysis system according to the invention is shown schematically and in two different orientations;

[0140] Fig. 6A and 6Bshows a further exemplary embodiment of a rotor of a valve according to the invention; and

[0141] Figure 7 Shown is a comparative example of the C4 detector signal obtained for a positioning plug during a two-dimensional separation. DETAILED DESCRIPTION

[0142] Figure 1 An exemplary embodiment of a valve 110 is shown in an exploded view. The valve 110 includes a stator 112, a rotor 114, and an actuator 116. The stator 112 includes a plurality of ports 118. The stator 112 can have a cylindrical shape. The actuator 116 can be operably connected to the rotor 114, and the stator 112 can be attached to the actuator 116 via screws 120. More details about the components of the valve can be provided in subsequent figures.

[0143] Figure 2A and 2B In perspective ( Figure 2A ) and top view ( Figure 2B ) shows an exemplary embodiment of a valve 110 according to the present invention. Figure 2A and 2B The valve 110 corresponds at least in part to Figure 1 Therefore, please refer to the above Figure 1 Description.

[0144] according to Figure 2A The valve 110 includes a plurality of ports 118. The plurality of ports 118 includes a plurality of groups 122 of ports 118. The group 122 of ports 118 includes a first group 124 of at least two first ports 126, a second group 128 of at least two second ports 130, and a third group 132 of at least two third ports 134. In addition, the group 122 of ports 118 may include a fourth group 136 of at least two fourth ports 138. In addition, the stator 112 may include a leak hole 140.

[0145] Port 118 may be capable of fluidly connecting to a passage of rotor 114. Further details regarding rotor 114 are provided below.

[0146] Figures 3A to 3C FIG. 1 shows an exemplary embodiment of a rotor 114 of a valve 110 according to the present invention. The valve 110 may correspond at least in part to a Figure 1 Valve or according to Figure 2A and 2B Therefore, please refer to the above Figure 1 as well as Figure 2A and 2B Description.

[0147] like Figures 3A to 3CThe rotor 114 is shown to be rotatable about an axis 142 of the rotor 114. Figures 3A to 3C The rotor 114 shown may be made of: at least one polymer material; a ceramic material; glass; at least one non-conductive material. Figures 3A to 3C The illustrated rotor 114 may have a cylindrical reinforced shape.

[0148] like Figures 3A to 3C The rotor 114 shown includes a plurality of channels 144. The plurality of channels includes at least one first channel 146 and at least one second channel 148. In addition, the plurality of channels may include at least one third channel 150.

[0149] like Figures 3A to 3C The passage 144 of the rotor 114 shown may be located at least partially on a virtual circle 152. The virtual circle 152 may be located on at least one surface 154 of the rotor 114. In particular, a center point 156 of the virtual circle 152 may correspond to the rotation axis 142 of the rotor 114. The passage 144 may have two ends 158, respectively. Figures 3A to 3C The ends 158 of the channels 144 may be located on the virtual circles 152 , respectively.

[0150] First passage 146 may have a first distance d1 to rotation axis 142 of rotor 114, and second passage 148 may have a second distance d2 to rotation axis 142. Third passage 150 may have a third distance d3 to rotation axis 142. First distance d1, second distance d2, and third distance d3 may be substantially equal.

[0151] The first channel 146 may include at least one first channel end 162, and the second channel 148 may include at least one second channel end 164. The first channel end 162 and the second channel end 164 may face each other. The distance d may be 4.33 mm.

[0152] In particular, according to Figure 3A The channels 144 of the rotor 114 may respectively correspond to the circle segments 160 of the virtual circle 152. Figure 3A The passage 144 of the rotor 114 may have a length α of 0.95 mm. Figure 3A The channels 144 of the rotor 114 may each have a volume of 10 nl. However, other volumes are also possible. Figure 3A The channel 144 of the rotor 114 may also have a volume of 20 nl or 40 nl.

[0153] In particular, according to Figure 3B The channels 144 of the rotor 114 may each have a semicircular shape. Figure 3BThe channels 144 of the rotor 114 may each have a volume of 20 nl. However, other volumes are also possible. Figure 3B The channel 144 of the rotor 114 may also have a volume of 10 nl or 40 nl.

[0154] In particular, according to Figure 3C The channels 144 of the rotor 114 may each have a semi-elliptical shape. Figure 3C The channels 144 of the rotor 114 may each have a volume of 40 nl. However, other volumes are also possible. Figure 3C The channel 144 of the rotor 114 may also have a volume of 20 nl or 10 nl.

[0155] Figures 4A to 4D FIG. 1 shows an exemplary embodiment of a rotor 114 of a valve 110 according to the present invention. The rotor 114 may correspond at least in part to a valve according to the present invention. Figures 3A to 3C Therefore, it can be referred to the above Figures 3A to 3B Description.

[0156] According to Figures 3A to 3C The rotor 114 is compared to Figures 4A to 4D The rotor 114 also includes a fourth passage 166. The fourth passage 166 may have a fourth distance d4 to the rotation axis 142. The first distance d1, the second distance d2, the third distance d3, and the fourth distance d4 may be substantially equal.

[0157] according to Figure 4A The channels 144 of the rotor may correspond to the circular segments 160 respectively and may have a volume of 10 nl. However, other volumes are also possible. Figure 4A The channel 144 of the rotor 114 may also have a volume of 20 nl or 40 nl. Figure 4A The passage 144 of the rotor 114 may have a length α of 0.95 mm. Figure 4B The channels 144 of the rotors may each have a semi-elliptical shape and may have a volume of 40 nl. Figure 4C The channels 144 of the rotors can each have a semicircular shape and can have a volume of 20 nl. However, other volumes are also possible. Figure 4C The channel 144 of the rotor 114 may also have a volume of 10 nl or 40 nl. Figure 4D The channels 144 of the rotors can each have a U-shape and can have a volume of 20 nl. However, other volumes are also possible. Figure 4D The channel 144 of the rotor 114 may also have a volume of 10nl or 40nl. Figure 4DIn the rotor, the first channel 146 may include a first channel end 162, and the second channel 148 may include a second channel end 164. The first channel end 162 and the second channel end 164 may face each other. The distance d may be greater than 1.0 mm. In particular, the distance d may be 3 mm.

[0158] according to Figures 4A to 4D The rotor 114 may exhibit mirror symmetry about an axis perpendicular to the rotation axis 142 of the rotor 114. Adjacent channels 144 may be equidistant from one another. Each channel 114 may be identically shaped.

[0159] Figure 5A and 5B An exemplary embodiment of an analysis system 170 according to the invention is shown schematically and in two different orientations. A rotor 114 is schematically depicted, which corresponds at least largely to the embodiment according to Figure 4A Therefore, referring to the above Figure 4A In addition, the port 118 of the stator 112 is schematically illustrated, although the stator 112 itself is not depicted. The rotor 114 includes a first passage 146 and a second passage 148. In addition, the rotor may include a third passage 150 and a fourth passage 166.

[0160] The analysis system 170 includes at least one analysis device 172. The analysis device 172 may be or may include a mass spectrometer, such as an ESI-QTOF-MS, for example. In addition, the analysis device 172 may include at least one sample separation device 174, such as an electromigration device. In addition, the analysis system 170 may include two syringe pumps 176 or any other liquid delivery system. In addition, the analysis system 170 may have a characterization unit 178, such as a UV detector located between the sample separation device 174 and one of the ports 118. The characterization unit 178 may be configured to characterize at least one property of the fluid, such as the velocity of the fluid flow.

[0161] exist Figure 5A , the rotor 114 is depicted in a loading orientation 180. In the loading orientation 180, a first fluid 182, in particular a sample 188, can be transferred into the first channel 146 via at least one of the first ports 126. In addition, a second fluid 184, such as MeOH, can be transferred into the second channel 148 via at least one of the second ports 130. In addition, a fourth fluid 186, such as a CTAB solution, can be transferred into the fourth channel 166 via at least one of the fourth ports 138.

[0162] exist Figure 5B , the rotor 114 is depicted in an injection orientation 190. Figure 4BIn the illustrated injection orientation 190, the fourth channel 166 is connected to the third ports 134 and the fourth fluid 186 can be transferred from the fourth channel 166 into one of the third ports 134. The first fluid 182 and the second fluid 184 have been injected into one of the third ports 134.

[0163] Fig. 6A and Figure 6B A further exemplary embodiment of a rotor 114 of a valve 110 according to the invention is shown. The rotor 114 may correspond at least partially to the Figure 4A Therefore, it can be referred to the above Figure 4A The additional grooves can serve as additional drainage for a liquid film that may spread between the rotor and the stator. In this way, current breakthrough between non-connected liquid channels can be prevented.

[0164] According to Figure 4A The rotor 114 is compared to Fig. 6A and 6B The rotor 114 also includes at least one cavity 192 configured to receive excess fluid. In particular, the cavity 192 can be implemented as a slit 194. Therefore, the cavity 192 can have a size in the sub-micron range and can therefore be micro-fabricated. Fig. 6A and 6B The rotor 114 may have four channels 144. Fig. 6A and 6B The rotor 144 may have four of the cavities 192. The cavities 192 and the channels 144 may be arranged in an alternating manner. Thus, one of the cavities 192 may be arranged between two adjacent channels 144. Fig. 6A Each of the cavities 192 of the rotor 114 may extend along a virtual line 196 extending between the center point 156 of the virtual circle 152 and a point of the virtual circle 152. Fig. 6A The cavities 192 of the rotor 114 may each extend radially relative to the center point 156 of the virtual circle 152. Figure 6BThe cavities 192 of the rotor 114 may extend transversely to the imaginary line 196. In particular, the cavities 192 may each include an outer end 198 and an inner end 200. The outer end 198 of the cavity 192 may be located on the outer imaginary square 202, and the inner end 200 of the cavity 192 may be located on the inner imaginary square 204. The outer imaginary square 202 and the inner imaginary square 204 may also have the center point 156 of the imaginary circle 152 as a center point. The outer imaginary square 202 may have a length l1, and the inner imaginary square 204 may have a length l2. The length l1 may be longer than the length l2. The outer imaginary square 202 and the inner imaginary square 204 may be twisted relative to each other.

[0165] Figure 7 A comparative example of the C4 detector signal obtained for a positioning plug during a two-dimensional detection is shown. The setup used to obtain this signal uses a conventional valve with a smaller number of ports and channels than described above. By using the sample loop of the valve as a syringe, the sample is transferred to the analytical device (CZE-QTOF-MS), i.e. there is no separation on the sample separation device (CE(SDS)-UV). In order to understand the requirements of a two-dimensional system, different volumes of methanol and cationic surfactant and their position relative to the sample were tested. A probe located 4 cm in front of the valve as an intermediate detector (Innovative Sensor Technology, Strasshof, Austria) ) allows determining the exact time when each zone is in the desired position. The decrease in conductivity is recorded as a negative peak, which corresponds to the zone where methanol and methanol:water (solvent for the cationic surfactant) pass through the C4D sensor. Therefore, C4D detection can be used for methanol and CTAB positioning while separation is being carried out in the sample separation device. Therefore, the transferred peaks do not wait for a long time in the sample loop and the analysis time of a complete two-dimensional run is reduced. The optimal conditions are methanol at 50 mbar for 12 seconds plus 0.4% (v / v) CTAB at 50 mbar for 20 seconds as the most flexible and effective conditions. In this way, considering the small short incision of the valve in two dimensions (approximately one-third of the volume of the sample loop -6.7nl), it is ensured that there is enough methanol before the sample and enough CTAB after the sample.

[0166] exist Figure 7In , the x-axis indicates time and the y-axis indicates the corresponding signal obtained. In particular, curve 206 indicates the signal obtained, line 208 indicates the conductivity σ at 200 mV, and line 210 indicates the maximum conductivity σmax. During the two-dimensional separation, a comparative example of the C4 detector signal 206 was obtained during the positioning of methanol (50 mbar for 10 seconds, corresponding to peak 212) and cationic surfactant (0.4% (w / v) CTAB (50 mbar for 20 seconds, corresponding to peak 214 of the SDS removal strategy) in methanol: water (50:50, v / v). The stop time for the positioning of the right plug has been calculated with the help of a spreadsheet. There, the time t1 of methanol at σ=200 mV corresponds to the right plug position, and for the calculation of the migration speed, it is necessary to state the time t2 of the CTAB plug at maximum conductivity, which corresponds to the end of the plug.

[0167] Furthermore, the migration time of the plug needs to be between 6 and 9 minutes and the total peak about 1 minute wide (capillary length is about 2×35 cm). This ensures that the plug is narrow enough for accurate positioning. If the plug is later than 10 minutes, peak broadening and less accurate positioning can be observed. Longer migration times are associated with higher back pressures in the capillary and / or valve. The system needs to be flushed with high pressure for several minutes.

[0168] If the plug is narrow enough and the injection volume is correct, another important indicator is the shape of the conductivity signal. The conductivity signal needs to drop to 0 for the methanol plug peak 212, and the CTAB plug should be a clear shoulder for the methanol peak 214. Both need to be ensured for correct plug positioning.

[0169] In the new valve design, the C4 detector is no longer required, however, it can be used to control the injection process.

[0170] Reference numerals list

[0171] 110 valve

[0172] 112 stator

[0173] 114 rotor

[0174] 116 Actuator

[0175] Port 118

[0176] 120 screws

[0177] 122 groups

[0178] 124 Group 1

[0179] 126 First Port

[0180] 128 Group 2

[0181] 130 Second port

[0182] 132 Group 3

[0183] 134 Third Port

[0184] 136 Group 4

[0185] 138 Fourth Port

[0186] 140 Leakage hole

[0187] 142 axis

[0188] 144 channels

[0189] 146 First Channel

[0190] 148 Second Channel

[0191] 150 Third Channel

[0192] 152 virtual circle

[0193] 154 Surface

[0194] 156 Center Point

[0195] 158 end

[0196] 160 Circle Segment

[0197] 162 First channel end

[0198] 164 Second channel end

[0199] 166 Fourth Channel

[0200] 168 axis

[0201] 170 Analysis System

[0202] 172Analysis device

[0203] 174 Sample separation device

[0204] 176 Syringe Pump

[0205] 178 Characterization Units

[0206] 180 loading orientation

[0207] 182 First Fluid

[0208] 184 Second Fluid

[0209] 186 The Fourth Fluid

[0210] 188 samples

[0211] 190 Injection Orientation

[0212] 192 Cavity

[0213] 194 Slit

[0214] 196 virtual lines

[0215] 198 outer end

[0216] 200 inner end

[0217] 202 External virtual square

[0218] 204 Internal virtual square

[0219] 206 Signal

[0220] Conductivity at 208200mV

[0221] 210 Maximum conductivity

[0222] 212 Peaks

[0223] 214 Peak

Claims

1. A valve (110) for transferring at least one fluid, comprising: At least one stator (112), wherein the stator (112) comprises a plurality of ports (118), the ports (118) comprising a plurality of groups (122) of ports (118), the plurality of groups (122) of ports (118) comprising a first group (124) of at least two first ports (126), a second group (128) of at least two second ports (130), and a third group (132) of at least two third ports (134); at least one rotor (114), wherein the rotor (114) comprises a plurality of channels (144), the channels (144) comprising at least one first channel (146) and at least one second channel (148), wherein the rotor (114) has a thickness of at least 1.5 mm; and At least one actuator (116), wherein the actuator (116) is operably connectable to the rotor (114); wherein the actuator (116) is configured to rotate the rotor (114) into at least one loading orientation (180), wherein in the loading orientation (180) one or both of the following conditions exist: a) the first channel (146) is connected to the first port (126) so that a first fluid (182) can be transferred into the first channel (146) via at least one of the first ports (126); b) the second channel (148) is connected to the second ports (130) such that a second fluid (184) can be transferred into the second channel (148) via at least one of the second ports (130); wherein the actuator (116) is further configured to rotate the rotor (114) into at least one first injection orientation and at least one second injection orientation, wherein in the first injection orientation, the first channel (146) is connected to the third ports (134) and the first fluid (182) is transferable from the first channel (146) to at least one of the third ports (134), and wherein in the second injection orientation, the second channel (148) is connected to the third ports (134) and the second fluid (184) is transferable from the second channel (148) to at least one of the third ports (134), The channel (144) is at least partially located on a virtual circle (152), wherein a center point (156) of the virtual circle (152) corresponds to a rotation axis (142) of the rotor (114), wherein the channel (144) has two ends (158), wherein the ends (158) are respectively located on the virtual circle (152), and wherein the channel (144) has a shape selected from the group consisting of: a semicircular shape, a semi-elliptical shape, and a U-shaped shape.

2. The valve (110) according to claim 1, wherein: Each of the channels (144) is designed so that when one of the channels (144) is connected to a corresponding group of ports (118), the channel (144) and the group of ports (118) form a loop, wherein the fluid can be transferred from at least one of the ports (118) of the group of ports (118) into the channel (144) and returned from the channel (144) to at least one other one of the ports of the group (122) of ports (118).

3. The valve (110) according to claim 1 or 2, wherein: The plurality of ports (118) further comprises at least one fourth group (136) of at least two fourth ports (138), wherein the passages (144) further comprises at least one fourth passage (166), wherein in the loading orientation (180) the following conditions exist: c) the fourth channel (166) is connected to the fourth port (138) so that a fourth fluid (186) can be transferred into the fourth channel (166); The actuator (116) is further configured to rotate the rotor (114) into at least one third injection orientation, wherein in the third injection orientation, the fourth fluid (186) is transferable from the fourth channel (166) to at least one of the third ports (134).

4. The valve (110) according to claim 1 or 2, wherein: At least one of the channels (144) has a volume of 1 nl to 500 nl.

5. The valve (110) according to claim 1 or 2, wherein: One or more of the channels (144) have a length of 0.5 mm to 5 mm.

6. The valve (110) according to claim 1 or 2, wherein: The first channel (146) includes at least one first channel end (162), wherein the second channel (148) includes at least one second channel end (164), wherein the first channel end (162) and the second channel end (164) face each other, and wherein a distance d between the first channel end (162) and the second channel end (164) is at least 1 mm.

7. The valve (110) according to claim 1 or 2, wherein: The first passage (146) has a first distance d1 to a rotation axis (142) of the rotor (114), wherein the second passage (148) has a second distance d2 to the rotation axis (142), wherein the first distance d1 and the second distance d2 are substantially equal.

8. An analysis system (170) for analyzing a sample, wherein: The analysis system (170) comprises the valve (110) according to any one of the preceding claims, wherein the analysis system (170) further comprises at least one analysis device (172) fluidically connectable to the two third ports (134).

9. The analysis system (170) according to claim 8, wherein: The analysis system (170) further comprises at least one sample separation device (174) fluidically connectable to the first port (126), wherein the analysis system (170) further comprises at least one characterization unit (178), wherein the characterization unit (178) is located between the sample separation device (174) and one of the first ports (126), wherein the characterization unit (178) is configured to characterize at least one property of the first fluid (182).

10. A method for transferring at least one fluid, the method using a valve (110) according to any one of claims 1 to 7, the method comprising the following steps: I. While the rotor (114) is in the loading orientation (180), perform one or both of the following steps: I.1 supplying the first fluid (182) into the first channel (146) while the first channel (146) is connected to the first port (126); I.2 supplying the second fluid (184) into the second channel (148) while the second channel (148) is connected to the second port (130); II. transferring the first fluid (182) to one of the third ports (134) by rotating the rotor (114) into the first injection orientation; III. Transferring the second fluid (184) to one of the third ports (134) by rotating the rotor (114) into the second injection orientation.

11. The method according to claim 10, wherein: The port (118) further comprises at least two fourth ports (138), wherein the channel (144) further comprises at least one fourth channel (166), wherein the method further comprises the following steps: I.3 supplying a fourth fluid (186) into the fourth passage (166) while the rotor (114) is in the loading orientation (180) and while the fourth passage (166) is connected to the fourth port (138); IV. The fourth fluid (186) is transferred to one of the third ports (134) by rotating the rotor (114) into a third injection orientation.

12. The method according to claim 11, wherein: The rotor (114) is rotated from the second injection orientation to a third injection orientation.

13. Use of the valve (110) according to any one of claims 1 to 7 for at least one purpose selected from the group consisting of: protein analysis and proteomics and mass spectrometry detection of metabolite analysis and metabolomics; electrically driven separation technology and connection of chromatographic separation to a mass spectrometer.

14. The use according to claim 13, wherein The proteomics includes protein charge variants and protein forms.

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