Patent Description:
Bioprocessing systems are widely used, e.g. to perform chemical separation. An example of a bioprocessing system is a chromatography system. Chromatography is a well-known procedure for analyzing and preparing chemical mixtures or chemical samples. The sample may typically be dissolved in a fluid, referred to as the mobile phase. The various sample components or samples of the mixture travel at different speeds, causing them to separate. In preparative chromatography the separation may be used to separate the sample components in a fractionation step where the mobile phase may be directed to different containers by a fraction collection unit.

The fraction collection unit will typically be controlled to divert flow of samples to different containers dependent on the output of a sensor/detector, e.g. an ultraviolet light absorbance detector.

The minimum volume of a sample that can be discriminated and/or diverted to a container is a fluid drop. The volume of such a drop depends on an outer diameter of a drop former or nozzle.

A problem with conventional solutions is that at low flow rates and/or narrow detector peaks (i.e. where a desired sample is only delivered for a brief moment in time) a very narrow tubing end is required, typically the tubing must be < <NUM> millimeters. For this dimension, the only readily available tubing is fused silica. This conventional drop former or nozzle has many disadvantages. It is difficult to handle as it is very fragile. Further, special cutting tools are required to adapt the fused silica tubing to a suitable length. Further, fused silica tubing has a relatively high price.

Thus, there is a need for an improved drop former or nozzle for a fraction collection unit.

An objective of embodiments of the present invention is to provide a solution which mitigates or solves the drawbacks and problems described above.

The above and further objectives are achieved by the subject matter described herein. Further advantageous implementation forms of the invention are further defined herein. According to the invention the objects of the invention is addressed by a nozzle assembly for a fraction collection unit configured to collect one or more fluid samples, said nozzle assembly comprising a conduit adapter configured to fluidly couple to a conduit and a nozzle body, wherein the nozzle body comprises at least a nozzle part configured to release drops of the one or more collected fluid samples at a tip of the nozzle part, and an interface part configured to mechanically couple the assembly to the fraction collection unit, wherein the assembly, when the conduit adapter is attached to the nozzle body, forms a fluid channel from an inlet of the conduit adapter to the tip of the nozzle part.

In one embodiment of the invention, an outer diameter of the tip of the nozzle part is in the range of <NUM>-<NUM> millimeters in diameter and more preferably in the range of <NUM>-<NUM> millimeters in diameter.

In one embodiment of the invention, the inner diameter of the tip of the nozzle part is preferably in the range of <NUM>-<NUM> millimeters in diameter and more preferably in the range of <NUM>-<NUM> millimeters in diameter.

In one embodiment of the invention the nozzle part comprises a cylindrical part and a conical part comprising the tip of the nozzle part.

In one embodiment of the invention, the interface part further comprises a gripping element configured to provide a secure grip for a user handling the nozzle assembly.

In one embodiment of the invention, the nozzle body and conduit adapter comprise attachment elements that are used to releasably attach the nozzle body to the conduit adapter.

In one embodiment of the invention, the nozzle assembly is made from plastic.

In one embodiment of the invention, the interface part further comprises a locking element configured to lock the nozzle assembly to the fraction collection unit.

In one embodiment of the invention, the interface part further comprises a collector interface part configured to be received by a recess of the fraction collection unit, wherein the locking element is provided at one end of the collector interface part which is arranged adjacent to the nozzle part.

In one embodiment of the invention, the locking element is formed like a flap extending from the collector interface part in a direction parallel to a centerline of the nozzle body, wherein the flap is provided with a locking lip at an end of the lip arranged furthest away from the collector interface part.

An advantage is that improved handling of the nozzle is provided as installation of tubing and nozzle can be made in two or more steps. A further advantage is that generic cutting tools can be used to adapt standard tubing to a suitable length. A further advantage is that cheap and easily available tubing can be used to fluidly couple the fraction collection unit to a sample source, such as a chromatography system.

Further applications and advantages of embodiments of the invention will be apparent from the following detailed description.

A more complete understanding of embodiments of the invention will be afforded to those skilled in the art, as well as a realization of additional advantages thereof, by a consideration of the following detailed description of one or more embodiments.

An "or" in this description and the corresponding claims is to be understood as a mathematical OR which covers "and" and "or", and is not to be understand as an XOR (exclusive OR). The indefinite article "a" in this disclosure and claims is not limited to "one" and can also be understood as "one or more", i.e., plural.

In the present disclosure the term "nozzle assembly" denotes an arrangement configured to be handled/held by a user and an arrangement in the form of a drop former or nozzle configured to receive fluid, typically from a conduit fluidly coupled to a fluid source, and dispense a drop of fluid and/or an arrangement configured to be held by fraction collection unit and typically moved to positions over different containers of the fraction collection unit.

In the present disclosure the terms "sensor" and "detector" are used interchangeably and denote an apparatus capable of detecting/sensing/measuring physical properties, e.g. of a fluid. In one example, a detector is a light absorbance apparatus, capable of measuring light absorbance of a fluid.

In the present disclosure the term "fluidly couple" denotes connecting two entities or units such that fluid can flow between the entities or units.

The present disclosure relates to a nozzle assembly which has both small outer diameter at the tip and a small inner diameter. The small outer diameter at the tip has the effect of generating drops of fluid with small volume. The small inner diameter has the effect of maintaining a high purity of the collected sample by ensuring that the desired compound is not diluted by the next separated compound. In other words, the nozzle assembly is provided with a relatively narrow, low internal volume, fluid channel between the conduit adapter/tubing connector and the end of the tip of the nozzle assembly.

This is e.g. the case for a chromatography system collecting compounds or samples with a "narrow peak", i.e. where the duration of an output peak from the detector has a relatively short duration in time. If the internal volume of the nozzle assembly is large, some of the sample/compound collected in a previous container will be dispensed into the current container and thus dilute the desired compound, a phenomenon sometimes denoted as peak-broadening.

The nozzle assembly further comprises two parts, optionally releasably attachable, namely a conduit adapter and a nozzle body. In some embodiments, the two parts are formed as one part having the same features as the two parts.

When the two parts are configured as releasably attachable parts, this has the advantage of allowing the user to separate the task of setting up a system, comprising a fluid source and fraction collection unit, into two steps: one step where the fluid source is connected to the conduit adapter and a second step where the nozzle body is installed into a fraction collection unit of the system. Further, the division of the nozzle assembly into two releasably attachable parts allows replacement of the nozzle body only, e.g. to a nozzle body with a different tip diameter/drop forming size. A further advantage is that the use of normal robust polyetereterketon PEEK tubing is possible instead of conventional systems typically using fragile fused silica tubing in the fraction collection unit.

In one exemplary embodiment the outer diameter of the tip of the nozzle assembly is <NUM> and the channel has an inner diameter of <NUM> with a total volume of <NUM>µl. In another exemplary embodiment the outer diameter of the tip of the nozzle assembly is <NUM> and the fluid channel is divided into two parts with a first part having an inner diameter of <NUM> and a second part having an inner diameter of <NUM>, with a total volume of <NUM>µl.

The nozzle is typically designed with different nozzle bodies to fit receiving recesses of various fraction collection units.

A brief description of the problem/challenge that is solved by this disclosure follows. To get small drops from the drop former/nozzle, the outer diameter of the tip of the drop former/nozzle needs to be relatively small. In one example with water in room temperature, the drop size in µl is ~<NUM>-20x the outer diameter of the tip of the drop former/nozzle in mm. To achieve drops with sizes < <NUM>µl, the outer diameter of the tip of the drop former/nozzle must be < <NUM>. In conventional systems, the drops are typically formed by the tubing end itself, i.e. the conduit/tubing fluidly coupling the fluid source to the fraction collection unit, so the outer diameter of the tubing must be < <NUM>. In this dimension, the only readily available tubing is fused silica. It has many disadvantages: it is very fragile, it needs special cutting tools, it has a relatively high price.

As mentioned above, by using the disclosed nozzle assembly with a conduit adapter configured for larger outer diameter conduits/tubing, such as standard PEEK <NUM>/<NUM>" (<NUM>). Such tubing is readily available, and normally used in the fluid sources and fraction collection units.

Technical and commercial advantages associated with the novel and unique features of this disclosure include that it is robust and easy to use, the small drop size and low internal volume results in low levels of peak-broadening and it can be produced at a relatively low cost.

<FIG> shows an exemplary application of a fraction collection unit according to one or more embodiments of the present disclosure. In this application the fraction collection unit is used in a bioprocessing system <NUM>, which may may comprise a selection of bioprocessing units, such as a reservoirs <NUM>, a column <NUM>, a detector <NUM> and the fraction collection unit <NUM>. The bioprocessing system <NUM> in the form of a chromatography apparatus <NUM> is described in further detail below.

The chromatography apparatus <NUM> may typically comprise at least one inlet <NUM>. The inlet may optionally be coupled to one or more reservoirs <NUM> configured to hold a fluid.

It is understood that the chromatography apparatus <NUM> may comprise any number of reservoirs and corresponding inlets. The inlet <NUM> may e.g. be implemented as tubular elements such as a tube or hose. The chromatography apparatus <NUM> may further comprise a controllable flow path unit (pumps and valves) <NUM>, a column <NUM> provided with fluid ports <NUM>-<NUM>. The column <NUM> may be comprised in the chromatography apparatus or arranged external to the chromatography apparatus.

The chromatography apparatus <NUM> may further comprise a control unit <NUM> which comprises circuitry, e.g. a processor and a memory. The memory may contain instructions executable by the processor, whereby said chromatography apparatus is operative to perform any of the steps or methods described herein. to direct the fraction collection unit <NUM> to different containers <NUM>-<NUM>.

The chromatography apparatus <NUM> may further optionally comprise the fraction collection unit <NUM>. The chromatography apparatus <NUM> is further fluidly coupled to the fraction collection unit <NUM>, thus typically providing samples for discrimination into different containers via the drop former or nozzle assembly disclosed herein.

It is noted that the present disclosure can be used with any application of fraction collection unit <NUM> and is not limited to chromatography.

<FIG> shows an isometric view of a conduit adapter <NUM> of the nozzle assembly <NUM> according to one or more embodiments of the present disclosure. In one embodiment, the conduit adapter <NUM> comprises a conduit interface part <NUM> and/or a grip part <NUM> and/or a body interface part <NUM>.

The conduit interface part <NUM> is typically configured to mechanically couple to a conduit and also fluidly couple to the conduit, thus allowing fluid to flow from the fluid source to the nozzle assembly. In one example, the conduit interface part <NUM> is formed with an slightly larger outer diameter than the inner diameter of the conduit, allowing the conduit to be mechanically coupled by friction when threaded over the conduit interface part <NUM> and simultaneously allowing the conduit to be fluidly coupled when the conduit and an inlet in the conduit interface part <NUM> form a fluid channel.

In one example, the top of the conduit interface part <NUM> is shaped like a conduit, with an outer diameter of <NUM> millimeters, an inner diameter of <NUM> millimeters and a height of <NUM> millimeters.

The grip part <NUM> is typically configured to provide a safe and secure grip of the conduit adapter <NUM>, when being held by a user. when the user is threading a conduit from the fluid source onto the conduit interface part <NUM>.

In one example, the grip part <NUM> is shaped like a ribbed cylinder, with an outer diameter of <NUM> millimeters and a height of <NUM> millimeters.

The body interface part <NUM> is typically configured to form a fluid channel and/or to releasably attach to the nozzle body <NUM> of the nozzle assembly <NUM>. The body interface part <NUM> may further optionally be provided with an attachment element <NUM>, such as threads, configured to releasably attach to the nozzle body <NUM> of the nozzle assembly <NUM>.

<FIG> shows a front view of the conduit adapter <NUM> of the nozzle assembly <NUM> according to one or more embodiments of the present disclosure. A section A-A is indicated by the central axis of the conduit adapter <NUM>.

<FIG> shows a section view of the conduit adapter <NUM> of the nozzle assembly <NUM> according to one or more embodiments of the present disclosure. The section shown is A-A, as indicated in <FIG>. As can be seen, a fluid channel <NUM> is formed from the inlet <NUM> in the conduit interface part <NUM> to the tip <NUM> of the conduit interface part <NUM>. The body interface part <NUM> is further optionally provided with an attachment element <NUM>, such as threads, configured to releasably attach to the nozzle body <NUM> of the nozzle assembly <NUM>.

In one example, the body interface part <NUM> has a total height/length of <NUM> millimeters, the attachment element <NUM> has a total height/length of <NUM> millimeters and is provided with UNF <NUM>-<NUM>2A threads. The fluid channel <NUM> formed from the inlet <NUM> to the tip <NUM> has an inner diameter of <NUM> millimeters. The inlet <NUM> is shaped like a cone having a diameter of <NUM> millimeters at the top and a diameter of <NUM> millimeters where it connects to the fluid channel <NUM>.

<FIG> shows an isometric view of the nozzle body <NUM> of the nozzle assembly <NUM> according to one or more embodiments of the present disclosure. In one embodiment, the nozzle assembly <NUM> comprises a nozzle part <NUM> and an interface part <NUM>.

In one further embodiment, the nozzle part <NUM> comprises a selection of any of a tip <NUM> and/or a cylindrical part <NUM> and/or a conical part <NUM>.

In one further embodiment, the interface part <NUM> comprises a selection of any of a grip part <NUM> and a collector interface part <NUM>. The grip part <NUM> is typically configured to provide a safe and secure grip of the nozzle body <NUM>, when being held/handled by a user. when the user is mounting the nozzle body <NUM> into the fraction collection unit <NUM>. The collector interface part <NUM> is typically configured to mechanically couple to the fraction collection unit <NUM>. provided with a shape corresponding to a receiving compartment/recess of the fraction collection unit <NUM>, such as a cylinder having a particular outer diameter.

<FIG> shows a front view of the nozzle body <NUM> of the nozzle assembly <NUM> according to one or more embodiments of the present disclosure. In one embodiment, the nozzle assembly <NUM> comprises the nozzle part <NUM> and the interface part <NUM>. A section A-A is illustrated along the centerline of the nozzle body <NUM>.

<FIG> shows a section view of the nozzle body <NUM> of the nozzle assembly <NUM> according to one or more embodiments of the present disclosure. The section shown is A-A, as indicated in <FIG>. In one embodiment, the nozzle body <NUM> is provided with a cavity or bore <NUM> having a corresponding shape to the body interface part <NUM> of the conduit adapter <NUM> and a fluid channel <NUM> fluidly coupling the cavity to the tip <NUM> of the nozzle part <NUM>. In one embodiment, the cavity or bore <NUM> is further optionally provided with an attachment element <NUM>, such as threads, configured to releasably attach to the conduit adapter <NUM> of the nozzle assembly <NUM>.

In one example, the total height/length of the nozzle body <NUM> is <NUM> millimeters. The total height/length of the collector interface part <NUM> is <NUM> millimeters. The total height/length of the nozzle part <NUM> is <NUM> millimeters. The total height/length of the grip part <NUM> is <NUM> millimeters. The inner diameter of the fluid channel <NUM> is <NUM> millimeters in a narrow part and <NUM> millimeters in a wider part of the fluid channel.

<FIG> shows the nozzle assembly <NUM> when the conduit adapter <NUM> is attached to the nozzle body <NUM> according to one or more embodiments of the present disclosure. A fluid channel is then formed from the inlet <NUM> of the conduit adapter <NUM> to the tip <NUM> of the nozzle part <NUM>.

A nozzle assembly <NUM> is provided for a fraction collection unit <NUM> configured to collect one or more fluid samples. The nozzle assembly <NUM> comprises a conduit adapter <NUM> configured to fluidly couple to a conduit. The conduit adapter <NUM> is further described in relation to <FIG>. In this embodiment, the nozzle assembly <NUM> further comprises a nozzle body <NUM> optionally configured to be releasably attached to the conduit adapter. The nozzle body <NUM> is further described in relation to <FIG>. In this embodiment, the nozzle body comprises at least a nozzle part <NUM> configured to release drops of the one or more collected fluid samples at a tip <NUM> of the nozzle part <NUM>, and an interface part <NUM> configured to mechanically couple the assembly <NUM> to the fraction collection unit. To mechanically couple may e.g. comprise the nozzle body at least partially being received by a recess of the fraction collection unit <NUM>. In this embodiment, the assembly, when the conduit adapter <NUM> is attached to the nozzle body <NUM>, forms a fluid channel from an inlet <NUM> of the conduit adapter <NUM> to the tip <NUM> of the nozzle part <NUM>.

In one example, a user may connect a conduit or tube to the conduit adapter <NUM> by threading the conduit or tube over a tube-shaped conduit interface part <NUM>. The user may then place the nozzle body <NUM>, or a collector interface part <NUM> of the nozzle body <NUM> into a recess of the fraction collection unit <NUM>. The user may then attach the conduit adapter <NUM> to the nozzle body <NUM> by inserting the body interface part <NUM> into the cavity or bore <NUM> and engage the attachment elements <NUM>, <NUM>, e.g. by rotating the conduit adapter <NUM> and engaging matching threads.

In one embodiment, an outer diameter of the tip <NUM> of the nozzle part <NUM> is in the range of <NUM>-<NUM> millimeters in diameter and more preferably in the range of <NUM>-<NUM> millimeters in diameter.

In one embodiment, the inner diameter of the tip <NUM> of the nozzle part <NUM> is preferably in the range of <NUM>-<NUM> millimeters in diameter and more preferably in the range of <NUM>-<NUM> millimeters in diameter.

In one embodiment, the nozzle part <NUM> comprises a cylindrical part <NUM> and a conical part <NUM> comprising the tip of the nozzle part.

In one embodiment, the interface part <NUM> further comprises a gripping element <NUM> configured to provide a secure grip for a user handling the nozzle assembly <NUM>.

In one embodiment, the nozzle body and conduit adapter comprise attachment elements <NUM>, <NUM> that are used to releasably attach the nozzle body to the conduit adapter. In one example the attachment elements <NUM>, <NUM> are UNF <NUM>-<NUM>2B threads. In one embodiment, the nozzle assembly <NUM> is made from plastic.

Claim 1:
A nozzle assembly (<NUM>) for a fraction collection unit (<NUM>) configured to collect one or more fluid samples, said nozzle assembly comprising and being characterized by:
a conduit adapter (<NUM>) configured to fluidly couple to a conduit, and
a nozzle body (<NUM>),
wherein the nozzle body comprises at least:
a nozzle part (<NUM>) configured to form and release drops of the one or more collected fluid samples at a tip (<NUM>) of the nozzle part (<NUM>), and
an interface part (<NUM>) configured to mechanically couple the assembly (<NUM>) to the fraction collection unit, wherein the assembly, when the conduit adapter (<NUM>) is attached to the nozzle body (<NUM>), forms a fluid channel from an inlet (<NUM>) of the conduit adapter (<NUM>) to the tip (<NUM>) of the nozzle part (<NUM>).