Patent Description:
In high performance liquid chromatography (HPLC), a liquid has to be provided usually at a very controlled flow rate (e. in the range of microliters to milliliters per minute) and at high pressure (typically <NUM>-<NUM> MPa, <NUM>-<NUM> bar, and beyond up to currently <NUM> MPa, <NUM> bar) at which compressibility of the liquid becomes noticeable. For liquid separation in an HPLC system, a mobile phase comprising a sample fluid (e.g. a chemical or biological mixture) with compounds to be separated is driven through a stationary phase (such as a chromatographic column packing), thus separating different compounds of the sample fluid which may then be identified. The term compound, as used herein, shall cover compounds which might comprise one or more different components.

The mobile phase, for example a solvent, is pumped under high pressure typically through a chromatographic column containing packing medium (also referred to as packing material or stationary phase). As the sample is carried through the column by the liquid flow, the different compounds, each one having a different affinity to the packing medium, move through the column at different speeds. Those compounds having greater affinity for the stationary phase move more slowly through the column than those having less affinity, and this speed differential results in the compounds being separated from one another as they pass through the column. The stationary phase is subject to a mechanical force generated in particular by a hydraulic pump that pumps the mobile phase usually from an upstream connection of the column to a downstream connection of the column. As a result of flow, depending on the physical properties of the stationary phase and the mobile phase, a relatively high pressure drop is generated across the column.

The mobile phase with the separated compounds exits the column and passes through a detector, which registers and/or identifies the molecules, for example by spectrophotometric absorbance measurements. A two-dimensional plot of the detector measurements against elution time or volume, known as a chromatogram, may be made, and from the chromatogram the compounds may be identified. For each compound, the chromatogram displays a separate curve feature also designated as a "peak". Efficient separation of the compounds by the column is advantageous because it provides for measurements yielding well defined peaks having sharp maxima inflection points and narrow base widths, allowing excellent resolution and reliable identification and quantitation of the mixture constituents. Broad peaks, caused by poor column performance, so called "Internal Band Broadening" or poor system performance, so called "External Band Broadening" are undesirable as they may allow minor components of the mixture to be masked by major components and go unidentified.

Fluidic couplers are widely used for providing a fluidic coupling between two or more fluidic components, e.g. for coupling a capillary to a device, for coupling two devices, et cetera. Such fluidic couplers may be used at various positions within the flow path e.g. within an HPLC system.

Planar microfluidic structures are described e.g. in <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, or <CIT>. <CIT> by the same applicant discloses fluidic coupling of planar fluidic structures. <CIT> describes two fluidic structures which can be pressed together thereby achieving a fluid tight seal.

It is an object of the invention to provide an improved fluidic coupling between fluidic structures, in particular for HPLC applications. The object is solved by the independent claim(s). Further embodiments are shown by the dependent claim(s).

A fluidic coupling is provided by and between a first fluidic structure and a second fluidic structure and being configured for fluidically coupling the first fluidic structure with the second fluidic structure. The first fluidic structure has a first channel configured for conducting fluid and opening at a first opening at a first surface of the first fluidic structure. The second fluidic structure has a second channel configured for conducting fluid and opening at a second opening at a second surface of the second fluidic structure. The fluidic coupling comprises a sealing element.

positioned between the first surface and the second surface. The first fluidic structure comprises a first elastic structure in and/or below the first surface. When the first surface and the second surface are pressed against each other, the first elastic structure is elastically deformed by the sealing element, the first opening and the second opening are in fluidic communication with each other, thus allowing a fluidic communication between the first channel and the second channel, and the sealing element is fluidically sealing the fluidic communication between the first channel and the second channel. This allows to provide a reliable fluidically sealing of the fluidic coupling, which also may be repeatable in a sense of allowing to repeatedly enable and disable the fluidic coupling e.g. by pressing together of and releasing pressure between the first fluidic structure and the second fluidic structure. Further, this may allow to avoid or at least reduce deformation of the sealing element.

In one embodiment, at least one of the first fluidic structure and the second fluidic structure is a planar structure. This allows providing a reliable and sealed coupling of planar structures, e.g. when applying microfluidic planar structures having extremely small physical dimensions, in particular of the channels for conducting fluid.

In one embodiment, the first fluidic structure is provided by a plurality of layers fixedly joined with each other, wherein the first channel is provided by a void between two of the plurality of layers. The layer structure allows providing the first elastic structure by adequately arranging, forming and structuring one or more of the plurality of layers.

In one embodiment, the second fluidic structure is provided by a plurality of layers fixedly joined with each other, wherein the second channel is provided by a void between two of the plurality of layers. The layer structure allows providing the second elastic structure by adequately arranging, forming and structuring one or more of the plurality of layers.

In one embodiment, at least one of the first fluidic structure and the second fluidic structure comprises or is comprised of one or more of the following materials: metal, in particular high-grade steel (e.g. <NUM>, MP35N, <NUM>), ceramics, in particular aluminum oxide, manganese oxide, zirconium oxide, aluminum nitrate, polymer, in particular PEEK, ULTEM, PEAK, PEKK, PEI, etc..

In one embodiment, the sealing element has a ring shape, preferably a concentric ring shape. This allows increasing in simplifying the sealing properties in that the sealing element is e.g. concentrically surrounding the respective opening of the respective fluidic structure.

In one embodiment, the sealing element is projecting beyond at least one of the first surface and the second surface, at least before pressing the first surface and the second surface against each other.

In one embodiment, the sealing element is part of or attached (e.g. fixed) to one of the first surface and the second surface, preferably by a pressing or dispensing procedure. Every suitable kind of attaching as known in the art can be applied, e.g. ranging from simply putting the sealing element on the respective surface, over fixing the sealing element to the respective surface e.g. by gluing, to dispensing (e.g. printing, sputtering, et cetera) the sealing element on the respective surface e.g. as part of a production process.

In one embodiment, the sealing element comprises or is comprised of one or more of the following materials: ductile and printable polymer compounds, in particular PEEK, ULTEM, PEAK, PEKK, PEI, etc..

In one embodiment, the first elastic structure is provided below an area of the first surface where the sealing element is abutting to the first surface when the first surface and the second surface are pressed against each other.

The first elastic structure is provided by a first membrane and a first void (e.g. channel, a hollow space, a cavity, a clearance or the like) below the first membrane. The first membrane is a part of the first surface, and the first membrane is elastically deformed into the first void when the first elastic structure is elastically deformed by the sealing element.

In one embodiment, the first void can be subjected to pressure, preferably by providing a pressurised fluid into the first void, in order to modify an elastic property of the first elastic structure. This may allow adjusting and/or controlling the elastic properties of the elastic structure, for example dependent on a pressure in the fluidic path of the first channel and the second channel. In one embodiment, the same fluid (e.g. a mobile phase in an HPLC system) flowing in the fluidic path of the first channel and the second channel is used for pressuring the void, which may lead to an automatic adjustment of the sealing force and/or properties dependent on the actual requirement for sealing.

In one embodiment, the second fluidic structure comprises a second elastic structure. This allows distributing deformation provided by the sealing element the first fluidic structure and the second fluidic structure and/or adjusting and/or controlling such deformation. The second elastic structure may be provided fully in accordance and substantially identical to the first elastic structure, e.g. in the sense of a symmetrical configuration, e.g. with the sealing element in between the first elastic structure and a second elastic structure.

In one embodiment, the second elastic structure is provided by a second membrane and a second void (e.g. channel, a hollow space, a cavity, a clearance or the like) below the second membrane. The second membrane is a part of the second surface, and the second membrane is elastically deformed into the second void when the second elastic structure is elastically deformed by the sealing element.

In one embodiment, the second void can be subjected to pressure, preferably by providing a pressurised fluid into the second void, in order to modify an elastic property of the second elastic structure. This may allow adjusting and/or controlling the elastic properties of the elastic structure, for example dependent on a pressure in the fluidic path of the first channel and the second channel. In one embodiment, the same fluid (e.g. a mobile phase in an HPLC system) flowing in the fluidic path of the first channel and the second channel is used for pressuring the void, which may lead to an automatic adjustment of the sealing force and/or properties dependent on the actual requirement for sealing.

In one embodiment, the fluidic coupling comprises a force applicator, such as a thread, a cam or an expanding medium, configured for pressing the first surface and the second surface against each other.

In one embodiment, the first opening and the second opening are adjacent to and substantially aligned with each other when the first surface and the second surface are pressed against each other.

In one embodiment, the sealing element is fluidically sealing the fluidic communication between the first channel and the second channel in a pressure range of up to <NUM> bar and beyond.

In one embodiment, at least one of the first fluidic structure and the second fluidic structure is a planar structure. The first fluidic structure is provided by a plurality of layers fixedly joined with each other, the first channel is provided by a first void between two of the plurality of layers, and the plurality of layers are preferably comprised of a metal material. The first surface is provided by an outer layer of the plurality of layers, and the first elastic structure is provided by a portion of the outer layer and a second void below the portion of the outer layer. The portion of the outer layer above the void is configured to act as a membrane being elastically deformable into the void when the first elastic structure is elastically deformed by the sealing element. Such embodiment can be provided using a so-called metal microfluidic (MMF) structure being a multilayer structure comprising two or more metal sheets bonded together e.g. by diffusion bonding, as described e.g. in the aforementioned <CIT> or in <CIT>, both by the same applicant.

In one embodiment, a separation system is provided for separating compounds of a sample fluid in a mobile phase. The fluid separation system comprises a mobile phase drive, preferably a pumping system, adapted to drive the mobile phase through the fluid separation system, a separation unit, preferably a chromatographic column, adapted for separating compounds of the sample fluid in the mobile phase, a first fluidic structure for conducting fluid, a second fluidic structure for conducting fluid, and a fluidic coupling (according to any of the aforementioned embodiments) for fluidically coupling the first fluidic structure with the second fluidic structure.

In one embodiment, the separation system further comprises at least one of: a sample dispatcher adapted to introduce the sample fluid into the mobile phase; a detector adapted to detect separated compounds of the sample fluid; a collection unit adapted to collect separated compounds of the sample fluid; a data processing unit adapted to process data received from the fluid separation system; and a degassing apparatus for degassing the mobile phase.

A method is provided for fluidically coupling a first fluidic structure with a second fluidic structure. The first fluidic structure has a first channel configured for conducting fluid and opening at a first opening at a first surface of the first fluidic structure. The second fluidic structure has a second channel configured for conducting fluid and opening at a second opening at a second surface of the second fluidic structure. The method comprises positioning a sealing element between the first surface and the second surface, and pressing the first surface and the second surface against each other, so that the sealing element will elastically deform an elastic structure in and/or below the first surface, the first opening and the second opening are in fluidic communication with each other, thus allowing a fluidic communication between the first channel and the second channel, and the sealing element is fluidically sealing the fluidic communication between the first channel and the second channel.

Embodiments of the present invention might be embodied based on most conventionally available HPLC systems, such as the Agilent <NUM>, <NUM> and <NUM> Infinity LC Series (provided by the applicant Agilent Technologies).

One embodiment of an HPLC system comprises a pumping apparatus having a piston for reciprocation in a pump working chamber to compress liquid in the pump working chamber to a high pressure at which compressibility of the liquid becomes noticeable.

One embodiment of an HPLC system comprises two pumping apparatuses coupled either in a serial or parallel manner. In the serial manner, as disclosed in <CIT>, an outlet of the first pumping apparatus is coupled to an inlet of the second pumping apparatus, and an outlet of the second pumping apparatus provides an outlet of the pump. In the parallel manner, an inlet of the first pumping apparatus is coupled to an inlet of the second pumping apparatus, and an outlet of the first pumping apparatus is coupled to an outlet of the second pumping apparatus, thus providing an outlet of the pump. In either case, a liquid outlet of the first pumping apparatus is phase shifted, preferably essentially by <NUM> degrees, with respect to a liquid outlet of the second pumping apparatus, so that only one pumping apparatus is supplying into the system while the other is intaking liquid (e.g. from the supply), thus allowing to provide a continuous flow at the output. However, it is clear that also both pumping apparatuses might be operated in parallel (i.e. concurrently), at least during certain transitional phases e.g. to provide a smooth(er) transition of the pumping cycles between the pumping apparatuses. The phase shifting might be varied in order to compensate pulsation in the flow of liquid as resulting from the compressibility of the liquid. It is also known to use three piston pumps having about <NUM> degrees phase shift. Also other types of pumps are known and operable in conjunction with the present invention.

The separating device preferably comprises a chromatographic column providing the stationary phase. The column might be a glass, metal, ceramic or a composite material tube (e.g. with a diameter from <NUM> to <NUM> and a length of <NUM> to <NUM>) or a microfluidic column (as disclosed e.g. in <CIT> or the Agilent <NUM> Series HPLC-Chip/MS System provided by the applicant Agilent Technologies. The individual components are retained by the stationary phase differently and separate from each other while they are propagating at different speeds through the column with the eluent. At the end of the column they elute at least partly separated from each other. During the entire chromatography process the eluent might be also collected in a series of fractions. The stationary phase or adsorbent in column chromatography usually is a solid material. The most common stationary phase for column chromatography is silica gel, followed by alumina. Cellulose powder has often been used in the past. Also possible are ion exchange chromatography, reversedphase chromatography (RP), affinity chromatography or expanded bed adsorption (EBA). The stationary phases are usually finely ground powders or gels and/or are microporous for an increased surface, which can be especially chemically modified, though in EBA a fluidized bed is used.

The mobile phase (or eluent) can be either a pure solvent or a mixture of different solvents. It can also contain additives, i.e. be a solution of the said additives in a solvent or a mixture of solvents. It can be chosen e.g. to adjust the retention of the compounds of interest and/or the amount of mobile phase to run the chromatography. The mobile phase can also be chosen so that the different compounds can be separated effectively. The mobile phase might comprise an organic solvent like e.g. methanol or acetonitrile, often diluted with water. For gradient operation water and organic is delivered in separate containers, from which the gradient pump delivers a programmed blend to the system. Other commonly used solvents may be isopropanol, THF, hexane, ethanol and/or any combination thereof or any combination of these with aforementioned solvents.

The sample fluid might comprise any type of process liquid, natural sample like juice, body fluids like plasma or it may be the result of a reaction like from a fermentation broth.

The fluid is preferably a liquid but may also be or comprise a gas and/or a supercritical fluid (as e.g. used in supercritical fluid chromatography - SFC - as disclosed e.g. in <CIT>).

The pressure in the mobile phase might range from <NUM>-<NUM> MPa (<NUM> to <NUM> bar), in particular <NUM>-<NUM> MPa (<NUM> to <NUM> bar), and more particular <NUM>-<NUM> MPa (<NUM> to <NUM> bar).

The HPLC system might further comprise a detector for detecting separated compounds of the sample fluid, a fractionating unit for outputting separated compounds of the sample fluid, or any combination thereof. Further details of HPLC system are disclosed with respect to the aforementioned Agilent HPLC series, provided by the applicant Agilent Technologies.

Embodiments of the invention can be partly or entirely embodied or supported by one or more suitable software programs, which can be stored on or otherwise provided by any kind of data carrier, and which might be executed in or by any suitable data processing unit. Software programs or routines can be preferably applied in or by the control unit.

In the context of this application, the term "fluidic sample" may particularly denote any liquid and/or gaseous medium, optionally including also solid particles, which is to be analyzed. Such a fluidic sample may comprise a plurality of fractions of molecules or particles which shall be separated, for instance biomolecules such as proteins. Since separation of a fluidic sample into fractions involves a certain separation criterion (such as mass, volume, chemical properties, etc.) according to which a separation is carried out, each separated fraction may be further separated by another separation criterion (such as mass, volume, chemical properties, etc.), thereby splitting up or separating a separate fraction into a plurality of sub-fractions.

In the context of this application, the term "fraction" may particularly denote such a group of molecules or particles of a fluidic sample which have a certain property (such as mass, volume, chemical properties, etc.) in common according to which the separation has been carried out. However, molecules or particles relating to one fraction can still have some degree of heterogeneity, i.e. can be further separated in accordance with another separation criterion.

In the context of this application, the term "sub-fractions" may particularly denote individual groups of molecules or particles all relating to a certain fraction which still differ from one another regarding a certain property (such as mass, volume, chemical properties, etc.). Hence, applying another separation criterion for the second separation as compared to the separation criterion for the first separation allows these groups to be further separated from one another by applying the other separation criterion, thereby obtaining the further separated sub-fractions.

In the context of this application, the term "downstream" may particularly denote that a fluidic member located downstream compared to another fluidic member will only be brought in interaction with a fluidic sample or its components after interaction of those with the other fluidic member (hence being arranged upstream). Therefore, the terms "downstream" and "upstream" relate to a general flowing direction of the fluidic sample or its components, but do not necessarily imply a direct uninterrupted fluidic connection from the upstream to the downstream system parts.

In the context of this application, the term "sample separation apparatus" may particularly denote any apparatus which is capable of separating different fractions of a fluidic sample by applying a certain separation technique. Particularly, two separation units may be provided in such a sample separation apparatus when being configured for a two-dimensional separation. This means that the sample or any of its parts or subset(s) is first separated in accordance with a first separation criterion, and is subsequently separated in accordance with a second separation criterion, which may be the same or different.

The term "separation unit" may particularly denote a fluidic member through which a fluidic sample is guided and which is configured so that, upon conducting the fluidic sample through the separation unit, the fluidic sample or some of its components will be at least partially separated into different groups of molecules or particles (called fractions or sub-fractions, respectively) according to a certain selection criterion. An example for a separation unit is a liquid chromatography column which is capable of selectively retarding different fractions of the fluidic sample.

In the context of this application, the terms "fluid drive" or "mobile phase drive" may particularly denote any kind of pump or fluid flow source or supply which is configured for conducting a mobile phase and/or a fluidic sample along a fluidic path. A corresponding fluid supply system may be configured for metering two or more fluids in controlled proportions and for supplying a resultant mixture as a mobile phase. It is possible to provide a plurality of solvent supply lines, each fluidically connected with a respective reservoir containing a respective fluid, a proportioning appliance interposed between the solvent supply lines and the inlet of the fluid drive, the proportioning appliance configured for modulating solvent composition by sequentially coupling selected ones of the solvent supply lines with the inlet of the fluid drive, wherein the fluid drive is configured for taking in fluids from the selected solvent supply lines and for supplying a mixture of the fluids at its outlet. More particularly, one fluid drive can be configured to provide a mobile phase flow which drives or carries the fluidic sample through a respective separation unit, whereas another fluid drive can be configured to provide a further mobile phase flow which drives or carries the fluidic sample or its parts after treatment by respective separation unit, through a further separation unit.

Other objects and many of the attendant advantages of embodiments of the present invention will be readily appreciated and become better understood by reference to the following more detailed description of embodiments in connection with the accompanied drawing(s). Features that are substantially or functionally equal or similar will be referred to by the same reference sign(s). The illustration in the drawing is schematically.

Referring now in greater detail to the drawings, <FIG> depicts a general schematic of a liquid separation system <NUM>. A pump <NUM> receives a mobile phase from a solvent supply <NUM>, typically via a degasser <NUM>, which degases the mobile phase and thus reduces the amount of dissolved gases in it. The pump <NUM> - as a mobile phase drive - drives the mobile phase through a separating device <NUM> (such as a chromatographic column) comprising a stationary phase. A sample dispatcher <NUM> (also referred to as sample introduction apparatus, sample injector, etc.) is provided between the pump <NUM> and the separating device <NUM> in order to subject or add (often referred to as sample introduction) portions of one or more sample fluids into the flow of a mobile phase (denoted by reference numeral <NUM>, see also <FIG>). The stationary phase of the separating device <NUM> is adapted for separating compounds of the sample fluid, e.g. a liquid. A detector <NUM> is provided for detecting separated compounds of the sample fluid. A fractionating unit <NUM> can be provided for outputting separated compounds of sample fluid.

While the mobile phase can be comprised of one solvent only, it may also be mixed of plurality of solvents. Such mixing might be a low pressure mixing and provided upstream of the pump <NUM>, so that the pump <NUM> already receives and pumps the mixed solvents as the mobile phase. Alternatively, the pump <NUM> might be comprised of plural individual pumping units, with plural of the pumping units each receiving and pumping a different solvent or mixture, so that the mixing of the mobile phase (as received by the separating device <NUM>) occurs at high pressure und downstream of the pump <NUM> (or as part thereof). The composition (mixture) of the mobile phase may be kept constant over time, the so called isocratic mode, or varied over time, the so called gradient mode.

A data processing unit <NUM>, which can be a conventional PC or workstation, might be coupled (as indicated by the dotted arrows) to one or more of the devices in the liquid separation system <NUM> in order to receive information and/or control operation. For example, the data processing unit <NUM> might control operation of the pump <NUM> (e.g. setting control parameters) and receive therefrom information regarding the actual working conditions (such as output pressure, flow rate, etc. at an outlet of the pump). The data processing unit <NUM> might also control operation of the solvent supply <NUM> (e.g. monitoring the level or amount of the solvent available) and/or the degasser <NUM> (e.g. setting control parameters such as vacuum level) and might receive therefrom information regarding the actual working conditions (such as solvent composition supplied over time, flow rate, vacuum level, etc.). The data processing unit <NUM> might further control operation of the sample dispatcher <NUM> (e.g. controlling sample introduction or synchronization of the sample introduction with operating conditions of the pump <NUM>). The separating device <NUM> might also be controlled by the data processing unit <NUM> (e.g. selecting a specific flow path or column, setting operation temperature, etc.), and send - in return - information (e.g. operating conditions) to the data processing unit <NUM>. Accordingly, the detector <NUM> might be controlled by the data processing unit <NUM> (e.g. with respect to spectral or wavelength settings, setting time constants, start/stop data acquisition), and send information (e.g. about the detected sample compounds) to the data processing unit <NUM>. The data processing unit <NUM> might also control operation of the fractionating unit <NUM> (e.g. in conjunction with data received from the detector <NUM>) and provides data back. Finally, the data processing unit might also process the data received from the system or its part and evaluate it in order to represent it in adequate form prepared for further interpretation.

Fluidic couplers are widely used for providing a fluidic coupling between two or more fluidic components, e.g. for coupling a capillary to a device, for coupling two devices, et cetera. Such fluidic couplers may be used at various positions within the flow path e.g. in the embodiment of <FIG> between the solvent supply <NUM> and the fractionating unit <NUM>. As an example, a fluidic coupler may be used for coupling a capillary leading from the degasser <NUM> to the pump <NUM>, a flow line (such as another capillary) from the pump <NUM> to the sample dispatcher <NUM>, another flow line (such as a microfluidic structure) between the sample dispatcher <NUM> and the separating device <NUM>, et cetera. It is clear and readily known in the art that such fluidic couplers may be used virtually at any position in a fluidic flow path were fluidic coupling between individual physical entities is required or useful.

<FIG> show schematically a fluidic coupler <NUM> according to the present invention. The fluidic coupler <NUM> comprises a first fluidic structure <NUM> and a second fluidic structure <NUM>, each being configured for conducting fluid and to be coupled with each other. <FIG> shows the fluidic coupler <NUM> in a three-dimensional representation with the first fluidic structure <NUM> being separated from the second fluidic structure <NUM>, i.e. in a state not yet being coupled together. <FIG> shows the fluidic coupler <NUM> in a two-dimensional cut-through representation corresponding to the non-coupled state of <FIG>. <FIG> shows the fluidic coupler <NUM> also in a two-dimensional cut-through representation (in accordance with <FIG>), however, in an assembled state providing a fluidic coupling between the first fluidic structure <NUM> and the second fluidic structure <NUM>.

The first fluidic structure <NUM> and the second fluidic structure <NUM>, as shown in <FIG>, may each be part of a respective fluidic device (and e.g. protruding laterally from such fluidic device) as indicated by respective break-through areas <NUM> and <NUM>. Such fluidic device may be any kind of device (or a part thereof) configured for handling fluid. In the exemplary embodiment of <FIG>, the first fluidic structure <NUM> and the second fluidic structure <NUM> shall each be a respective fluidic conduit configured for conducting fluid. The first fluidic structure <NUM> and/or the second fluidic structure <NUM> may extend beyond the respective break-through areas <NUM> and <NUM>. Alternatively, the first fluidic structure <NUM> and/or the second fluidic structure <NUM> may extend as a respective connecting piece from a respective fluidic device in order to provide a connection and/or fluidic coupling of the respective fluidic device e.g. to another fluidic device.

In the embodiment of <FIG>, both of the first fluidic structure <NUM> (best visible in <FIG>) and the second fluidic structure <NUM> are provided as planar structures. The first fluidic structure <NUM> has a circular contour <NUM> and comprises a first fluid port <NUM> (best visible in <FIG>) located at the center of a contact surface <NUM>. The location of the first fluid port <NUM> is preferably in a predefined relationship with the contour <NUM>. The first fluid port <NUM> is fluidically connected with a fluid channel <NUM> (indicated by dashed lines in <FIG>) which may provide a fluidic connection between the fluid port <NUM> and the (not shown) fluidic device.

The second fluidic structure <NUM> (also) has a circular contour <NUM> (best visible in <FIG>) and comprises a second fluid port <NUM> (best visible in <FIG>) located at the center of a contact surface <NUM>. The location of the second fluid port <NUM> is (also) preferably in a predefined relationship with the contour <NUM>. The second fluid port <NUM> is fluidically connected with a fluid channel <NUM> (not visible in <FIG>) which may provide a fluidic connection between the fluid port <NUM> and the (not shown) fluidic device.

The first fluidic structure <NUM> is adapted for being pressed against another planar coupling member of another fluidic device such as the second fluidic structure <NUM>. Thus, a fluidic connection is established between the fluid ports <NUM> and <NUM> of the two planar coupling members of the first fluidic structure <NUM> and the second fluidic structure <NUM>.

The first fluidic structure <NUM> and/or the second fluidic structure <NUM> may for example be realized as a multilayer structure comprising two or more sheets, preferably of metal or plastic, which may preferably be bonded together e.g. by diffusion bonding.

For example, the first fluidic structure <NUM> and/or the second fluidic structure <NUM> may be realized as a so-called metal microfluidic (MMF) structure being a multilayer structure comprising two or more metal sheets bonded together e.g. by diffusion bonding, as described e.g. in the aforementioned <CIT> or <CIT>, both by the same applicant.

The planar first fluidic structure <NUM> is made of three metal sheets <NUM>, <NUM>, <NUM>, as best visible in <FIG>. The planar second fluidic structure <NUM> may also be made of three metal sheets <NUM>, <NUM>, <NUM>, as best visible in <FIG>. The metal sheets <NUM>-<NUM>, <NUM>-<NUM> may for example be titanium sheets or stainless steel sheets, e.g. with a thickness of about <NUM> up to single digit millimeter regions. For processing the metal sheets <NUM>-<NUM>, <NUM>-<NUM>, techniques like e.g. electrochemical or chemical milling may be employed. Electrochemical or chemical milling may e.g. be used for forming the outer contour of the metal sheets, or for forming the fluid channels <NUM>, <NUM>, or for forming both the outer contour and the fluid channel. Alternatively, the fluid channels <NUM>, <NUM> may be formed by cutting a groove e.g. into the (middle) metal sheet <NUM>, <NUM>. Further alternatively, the fluid channels <NUM>, <NUM> may be formed by using a stamping process. The fluid ports <NUM>, <NUM> may be formed by cutting a via hole into the respective (outer) metal sheet <NUM>, <NUM>. When provided in MMF structure, the fluid ports <NUM>, <NUM> may have a diameter in the range of <NUM>-<NUM>.

After the metal sheets <NUM>-<NUM>, and respectively the metal sheets <NUM>-<NUM>, have been processed, they may be bonded with each other. According to a preferred embodiment, diffusion welding is used for bonding the metal sheets. In diffusion welding, a multilayer structure comprising two or more stacked metal sheets is put in a vacuum oven for several hours, whereby the metal sheets are pressed against one another with a contact pressing force. Preferably, the stack of metal sheets is subjected to a temperature below the melting point, and preferably to a temperature between <NUM> and <NUM> depending on the metals to be bonded. By applying heat, vacuum and a contact pressing force to the stack of metal sheets, diffusion of the metal atoms is enhanced, and strong covalent bonds are formed between adjacent metal sheets. As a result, a multilayer structure with a fluid tight fluidic channel can be obtained.

Turning back to <FIG>, the second fluidic structure <NUM> further comprises a sealing element <NUM>, which in the shown embodiment has a ring shape and is located concentrically around the second fluid port <NUM>. As best visible in <FIG>, the sealing elements <NUM> is protruding beyond the contact surface <NUM> of the second fluidic structure <NUM>, as indicated by X. The height X is preferably selected to be smaller than a height Y of the second fluidic structure <NUM>, and more preferably X is to be significantly smaller than Y. The sealing element <NUM> is arranged and configured to provide a fluidic sealing when the first fluidic structure <NUM> and the second fluidic structure <NUM> are pressed against each other (as shown in <FIG>), so that the fluid ports <NUM> and <NUM> are opening into each other in a fluid tight manner.

The second fluidic structure <NUM> further comprises an elastic structure <NUM> below the sealing element <NUM>. The elastic structure <NUM> is provided to be elastically deformed by the sealing element <NUM>, when the first fluidic structure <NUM> and the second fluidic structure <NUM> are pressed against each other (as shown in <FIG>).

In the exemplary embodiment of <FIG>, the elastic structure <NUM> is provided by a void <NUM> e.g. in the metal sheet <NUM>. The void <NUM> is preferably provided below the entire area where the sealing element <NUM> abuts or attaches to the contact surface <NUM>. In the shown embodiment of <FIG>, wherein the sealing element <NUM> has a ring shape and is located concentrically around the second fluid port <NUM>, also the void <NUM> has a ring shape and is located concentrically around the second fluid port <NUM>.

The part of the metal sheet <NUM> between the void <NUM> and the contact surface <NUM> acts as a membrane <NUM> which can be deformed by the sealing element <NUM> into the void <NUM>, e.g. when the first fluidic structure <NUM> and the second fluidic structure <NUM> are pressed against each other (as shown in <FIG>).

The elastic structure <NUM> is preferably designed that the deformation of the membrane <NUM> as provided by the sealing element <NUM> is substantially elastic, preferably without or only minimal plastic deformation.

In the exemplary embodiment of <FIG>, the void <NUM> is designed to be broader than the area where the sealing element <NUM> abuts to the contact surface <NUM>. In <FIG>, the area where the sealing element <NUM> abuts to the contact surface <NUM> is indicated by an arrow <NUM>, while the breadth of the void <NUM> is indicated by an arrow <NUM>.

As further shown in <FIG>, also the first fluidic structure <NUM> may comprise another elastic structure <NUM> in an area of the contact surface <NUM> where the sealing element <NUM> will abut or is abutting. The elastic structure <NUM> is also provided to be elastically deformed by the sealing element <NUM> when the first fluidic structure <NUM> and the second fluidic structure <NUM> are pressed against each other (as shown in <FIG>).

In the exemplary embodiment of <FIG>, the elastic structure <NUM> is provided by a void <NUM> in the metal sheet <NUM>. The void <NUM> is preferably provided below the entire area where the sealing element <NUM> abuts or attaches to the contact surface <NUM>. The part of the metal sheet <NUM> between the void <NUM> and the contact surface <NUM> acts as a membrane <NUM> which can be deformed by the sealing element <NUM> into the void <NUM>, e.g. when the first fluidic structure <NUM> and the second fluidic structure <NUM> are pressed against each other (as shown in <FIG>).

In the exemplary embodiment of <FIG>, the void <NUM> is designed to be broader than the area where the sealing element <NUM> abuts to the contact surface <NUM>. In <FIG>, the breadth of the void <NUM> is indicated by an arrow <NUM>.

As schematically illustrated in <FIG>, when the first fluidic structure <NUM> and the second fluidic structure <NUM> are pressed against each other, the sealing element <NUM> will deform both membranes <NUM> and <NUM>. This allows that the contact surfaces <NUM> and <NUM> can at least partly abut to each other, preferably at least in an area around where the first fluid port <NUM> opens into the second fluid port <NUM> in order to provide a fluid tight coupling between the first fluid port <NUM> and the second fluid port <NUM>, as indicated by the arrows in <FIG>. This also allows to avoid or at least reduce a dead volume. Such dead volume may be generated when the first fluid port <NUM> and the second fluid port <NUM> are not fully opening into each other but also into a space between the contact surfaces <NUM> and <NUM>.

While the exemplary embodiment of <FIG> shows the first fluidic structure <NUM> having the elastic structure <NUM> as well as the second fluidic structure <NUM> having the elastic structure <NUM>, it is clear that a fluid tight coupling can also be provided with only one of the elastic structures <NUM>, <NUM>. Accordingly, plural elastic structures may be applied into a respected fluidic structure.

The elastic properties of the elastic structures <NUM>, <NUM> can be designed in controlled e.g. by the geometry of the respective void <NUM>, <NUM> (such as the breadth <NUM>, <NUM>), the thickness and/or shape of the membrane <NUM>, <NUM>, the material(s) of the membrane <NUM>, <NUM>, et cetera.

Sealing properties between the first fluidic structure <NUM> and the second fluidic structure <NUM> may also be designed and/or improved by selecting the material of and/or by providing a coating on at least one of the contact surfaces <NUM>, <NUM>.

The elastic structures <NUM>, <NUM> (or at least one of these) allow to avoid or reduce squeezing, crushing, creeping and/or flowing of the sealing element <NUM> when the first fluidic structure <NUM> and the second fluidic structure <NUM> are pressed against each other.

The fluidic coupler <NUM> allows a preferably repeatable coupling and detaching of the first fluidic structure <NUM> and the second fluidic structure <NUM>. The elastic structures <NUM>, <NUM> (or at least one of these) allow that the fluid tight sealing can be remained even after multiple coupling and detaching.

The sealing element <NUM> is preferably made of a polymer material, such as PTFE, PEEK or similar. Alternatively, noble metals, such as gold, may also be applied.

While the exemplary embodiment of <FIG> shows the sealing element <NUM> being attached to or part of the second fluidic structure <NUM>, the sealing element <NUM> may also be attached to or part of the first second fluidic structure <NUM>. Alternatively, the sealing element <NUM> may be a loose part which may be inserted - on demand - between the first fluidic structure <NUM> and the second fluidic structure <NUM>.

The voids <NUM>, <NUM> may be provided e.g. by an etching process or by otherwise removing a portion of the respective sheet.

The voids <NUM>, <NUM> are preferably provided not being in any fluidic contact with the fluid channels <NUM>, <NUM>, ensuring a strict separation to the fluid flow in the fluid channels <NUM>, <NUM>.

In one embodiment, at least one of the voids <NUM>, <NUM> is coupled to a source of pressure allowing to adjust the elastic properties of the respective elastic structures <NUM>, <NUM>. Such source of pressure may be a pump or a fluid supplied into the void. In one embodiment in the liquid separation system <NUM> e.g. of <FIG>, at least one of the voids <NUM>, <NUM> is fluidically coupled to or supplied by the mobile phase is driven by the pump <NUM>. This allows increasing the elastic pressure on the sealing elements <NUM> with an increase of pressure in the mobile phase, and the other way around.

It is clear that the concept of the fluidic coupler <NUM> has shown in <FIG> is not limited to the shown exemplary embodiment. As an example, instead of two planar structures, only one of the first fluidic structure <NUM> and the second fluidic structure <NUM> may be provided as a planar structure. Alternatively, neither of the first fluidic structure <NUM> and the second fluidic structure <NUM> may be provided as planar structure.

While the concept of the fluidic coupler <NUM> works exceptionally well for fluidically coupling planar structures, it is sufficient that the respective contact areas (such as the contact area are <NUM> and <NUM> in <FIG>) where the coupling of the first fluidic structure <NUM> and the second fluidic structure <NUM> is to be provided is sufficiently plain to allow abutting of the contact areas.

Further, the concept of the fluidic coupler <NUM> is not limited for only providing a single fluidic coupling between adjacent fluid ports (such as the first fluid port <NUM> and the second fluid port <NUM> in <FIG>), but also plural fluidic couplings may be provided and accomplished.

<FIG> show a few exemplary embodiments according to the present invention.

<FIG> shows a fluidic structure <NUM> having two fluid ports <NUM> and <NUM>, each being surrounded by a respective sealing element <NUM> and <NUM>. The fluidic structure <NUM> may be used to couple with one or two individual fluidic structures, such as or similar to the first fluidic structure <NUM> and the second fluidic structure <NUM> of <FIG>. Alternatively, the fluidic structure <NUM> may couple to a fluidic structure (not shown) being similarly designed as the fluidic structure <NUM> and also having two ports to provide a fluidic coupling with the fluid ports <NUM> and <NUM>. As explained in the foregoing, at least one of the fluidic structures to be coupled to needs to provide a respective elastic structure to be elastically by the respective sealing element when pressing the two fluidic structures against each other.

<FIG> illustrates an embodiment of the fluidic structure <NUM> similar to the embodiment in <FIG>, however, with four fluid ports <NUM>, <NUM>, <NUM>, and <NUM>, each surrounded by a respective sealing element <NUM>, <NUM>, <NUM>, and <NUM>.

<FIG> illustrates an embodiment of the fluidic structure <NUM> similar to the embodiments in <FIG>, however, with seven fluid ports <NUM>-<NUM>, each surrounded by a respective sealing element <NUM>-<NUM>. In contrast to the longitudinal arrangement of the fluid ports in the embodiments of <FIG>, the fluid ports <NUM>-<NUM> are arranged in a circular manner.

Claim 1:
A fluidic coupling (<NUM>) provided by and between a first fluidic structure (<NUM>) and a second fluidic structure (<NUM>) and being configured for fluidically coupling the first fluidic structure (<NUM>) with the second fluidic structure (<NUM>), wherein
the first fluidic structure (<NUM>) has a first channel (<NUM>) configured for conducting fluid and opening at a first opening (<NUM>) at a first surface (<NUM>) of the first fluidic structure (<NUM>),
the second fluidic structure (<NUM>) has a second channel (<NUM>) configured for conducting fluid and opening at a second opening (<NUM>) at a second surface (<NUM>) of the second fluidic structure (<NUM>),
the fluidic coupling (<NUM>) comprises a sealing element (<NUM>) positioned between the first surface (<NUM>) and the second surface (<NUM>), and
the first fluidic structure (<NUM>) comprises a first elastic structure (<NUM>) in and/or below the first surface (<NUM>),
wherein, when the first surface (<NUM>) and the second surface (<NUM>) are pressed against each other,
the first elastic structure (<NUM>) is elastically deformed by the sealing element (<NUM>),
the first opening (<NUM>) and the second opening (<NUM>) are in fluidic communication with each other, thus allowing a fluidic communication between the first channel (<NUM>) and the second channel (<NUM>), and
the sealing element (<NUM>) is fluidically sealing the fluidic communication between the first channel (<NUM>) and the second channel (<NUM>);
wherein the first elastic structure (<NUM>) is provided by a first membrane (<NUM>) and a first void (<NUM>) below the first membrane (<NUM>), wherein the first membrane (<NUM>) is a part of the first surface (<NUM>); and
wherein the first membrane (<NUM>) is elastically deformed into the first void (<NUM>) when the first elastic structure (<NUM>) is elastically deformed by the sealing element (<NUM>).