Nozzle assembly for a fraction collection unit

Abstract

The present invention relates to a nozzle assembly 200 for a fraction collection unit 120 configured to collect one or more fluid samples, the nozzle assembly comprising a conduit adapter 210 configured to fluidly couple to a conduit, and a nozzle body 220, the nozzle body comprising at least a nozzle portion 221 configured to eject droplets of one or more collected fluid samples at a tip 223 of the nozzle portion 221, and an interface portion 222 configured to mechanically couple the assembly 200 to the fraction collection unit, the assembly forming a fluid channel from an inlet 219 of the conduit adapter 210 to the tip 223 of the nozzle portion 221 when the conduit adapter 210 is attached to the nozzle body 220.

Description

[Technical Field]

[0001] The present invention relates to a nozzle assembly for a fraction collection unit configured to collect one or more fluid samples. [Background technology]

[0002] Bioprocessing systems are widely used, for example, to perform chemical separations. One example of a bioprocessing system is a chromatography system. Chromatography is a well-known procedure for analyzing and preparing chemical mixtures or samples. Typically, the sample may be dissolved in a fluid called a mobile phase. The various sample components or mixture samples migrate at different rates, thereby resulting in separation. In preparative chromatography, this separation may be utilized to separate the sample components in a fractionation step, during which the mobile phase may be pumped into separate containers by a fraction collection unit.

[0003] Typically, the fraction collection unit is controlled to split the sample stream into different containers based on the output of a sensor / detector, such as an ultraviolet absorbance detector.

[0004] The smallest volume of sample that can be distinguished and / or diverted to a container is a fluid droplet, the volume of which is determined by the outer diameter of the droplet former or nozzle.

[0005] A problem with conventional solutions is that low flow rates and / or short detector peaks (i.e., the desired sample is delivered for only a fraction of a second) require very thin tube ends, typically less than 0.5 millimeters. The only readily available tube at this size is fused silica. This conventional droplet former or nozzle has a number of drawbacks. Conventional droplet formers or nozzles are very fragile and therefore difficult to handle. Furthermore, specialized cutting tools are required to trim the fused silica tube to the appropriate length. Furthermore, fused silica tubes are relatively expensive.

[0006] Therefore, there is a need for an improved droplet former or nozzle for a fraction collection unit. Summary of the Invention [Problem to be solved by the invention]

[0007] It is an object of embodiments of the present invention to provide a solution that alleviates or eliminates the above-mentioned drawbacks and problems. [Means for solving the problem]

[0008] These and other objects are achieved by the subject matter described herein, wherein further advantageous implementations of the invention are further defined.

[0009] According to a first aspect of the present invention, these objects of the present invention are addressed by a nozzle assembly for a fraction collection unit configured for collecting one or more fluid samples, said nozzle assembly comprising a conduit adapter configured for fluid coupling to a conduit, and a nozzle body, the nozzle body comprising at least a nozzle portion configured to eject droplets of the one or more collected fluid samples at a tip of the nozzle portion, and an interface portion configured to mechanically couple the assembly to the fraction collection unit, the assembly forming a fluid channel from an inlet of the conduit adapter to the tip of the nozzle portion when the conduit adapter is attached to the nozzle body.

[0010] In one embodiment of the first aspect of the present invention, the outer diameter of the tip of the nozzle portion is in the range of 0.2 to 2 mm, and more preferably in the range of 0.3 to 0.5 mm.

[0011] In one embodiment of the first aspect of the present invention, the inner diameter of the nozzle portion is preferably in the range of 0.1 to 1 mm, and more preferably in the range of 0.2 to 0.4 mm.

[0012] In one embodiment of the first aspect of the present invention, the nozzle portion comprises a cylindrical part and a conical part that comprises the tip of the nozzle portion.

[0013] In one embodiment of the first aspect of the present invention, the interface portion further comprises a grip element configured to provide a secure grip for a user to handle the nozzle assembly.

[0014] In one embodiment of the first aspect of the invention, the nozzle body and the conduit adaptor comprise an attachment element used to removably attach the nozzle body to the conduit adaptor.

[0015] In one embodiment of the first aspect of the present invention, the nozzle assembly is made from plastic.

[0016] In an embodiment of the first aspect of the present invention, the interface portion further comprises a locking element configured to lock the nozzle assembly relative to the fraction collection unit.

[0017] In an embodiment of the first aspect of the present invention, the interface portion further comprises a collector interface portion configured to be received by a recess of the fraction collection unit, and the locking element is provided at one end of the collector interface portion arranged adjacent to the nozzle portion.

[0018] In one embodiment of the first aspect of the invention, the locking element is formed as a flap extending from the collector interface portion in a direction parallel to the midline of the nozzle body, the flap comprising a locking lip at the end of the lip located furthest from the collector interface portion.

[0019] One advantage of the embodiment according to the first aspect is that it allows for tubing and nozzle installation in two or more steps, thereby improving nozzle handling. Another advantage is that it allows standard tubing to be cut to the appropriate length using common cutting tools. A further advantage is that it allows for the use of inexpensive, readily available tubing to fluidly couple the fraction collection unit to a sample source, such as a chromatography system.

[0020] Other applications and advantages of embodiments of the present invention will become apparent from the following detailed description. [Brief explanation of the drawings]

[0021] [Figure 1] FIG. 1 illustrates one application of a fraction collection unit according to one or more embodiments of the present disclosure. [Figure 2A] 1 illustrates a conduit adapter of a nozzle assembly according to one or more embodiments of the present disclosure. [Figure 2B]1 illustrates a conduit adapter of a nozzle assembly according to one or more embodiments of the present disclosure. [Figure 2C] 1 illustrates a conduit adapter of a nozzle assembly according to one or more embodiments of the present disclosure. [Figure 3A] FIG. 1 illustrates a nozzle body of a nozzle assembly according to one or more embodiments of the present disclosure. [Figure 3B] FIG. 1 illustrates a nozzle body of a nozzle assembly according to one or more embodiments of the present disclosure. [Figure 3C] FIG. 1 illustrates a nozzle body of a nozzle assembly according to one or more embodiments of the present disclosure. [Figure 4] 1 illustrates a nozzle assembly with a conduit adapter attached to the nozzle body in accordance with one or more embodiments of the present disclosure. [Figure 5] 10A-10C illustrate a nozzle assembly further comprising a locking element according to one or more embodiments of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0022] Those skilled in the art will gain a fuller understanding of embodiments of the present invention and a realization of further advantages thereof by reviewing the following detailed description of one or more embodiments, it being understood that like reference numerals are used to identify like elements shown in one or more of the drawings.

[0023] In this description and the corresponding claims, "or" should be understood as the mathematical "OR," which includes "and" and "or," and not as an XOR (exclusive or). In this disclosure and claims, the indefinite article "a" is not limited to "one" but can also be understood as "one or more," i.e., plural.

[0024] In this disclosure, the term "nozzle assembly" refers to a composition configured to be handled / held by a user, typically in the form of a droplet former or nozzle configured to receive fluid from a conduit fluidly coupled to a fluid source and dispense fluid droplets, and / or a composition configured to be held by a fraction collection unit and typically moved to positions over various receptacles of the fraction collection unit.

[0025] In this disclosure, the terms "sensor" and "detector" are used interchangeably to refer to a device capable of detecting / sensing / measuring a physical property of, for example, a fluid. In one example, the detector is a light absorption device capable of measuring the absorbance of a fluid.

[0026] In this disclosure, the term "fluidly couple" refers to connecting two entities or units in such a way that fluid can flow between them.

[0027] The present disclosure relates to a nozzle assembly having both a small outer diameter and a small inner diameter at its tip. The small outer diameter at the tip has the effect of generating small-volume fluid droplets. The small inner diameter has the effect of maintaining high purity of the collected sample by ensuring that the desired component is not diluted by subsequent separate components. In other words, the nozzle assembly includes a relatively narrow, low-internal-volume fluid channel between the conduit adapter / tubing connector and the end of the tip of the nozzle assembly.

[0028] For example, this is the case in chromatographic systems that collect components or samples in "short peaks," i.e., when the duration of the detector output peak is relatively short. If the internal volume of the nozzle assembly is large, some of the sample / component collected in the previous container will be dispensed into the current container, thus diluting the desired component; this phenomenon is sometimes referred to as peak broadening.

[0029] The nozzle assembly further comprises two optionally removably attachable parts, the conduit adapter and the nozzle body, which in some embodiments are formed as a single part having identical features in the two parts.

[0030] When these two parts are configured as detachable, attachable parts, this has the advantage that the user can divide the task of building a system consisting of a fluid source and a fraction collection unit into two steps: a first step in which the fluid source is connected to the conduit adapter, and a second step in which the nozzle body is installed in the fraction collection unit of the system. Furthermore, by dividing the nozzle assembly into two detachable, attachable parts, it becomes possible to replace only the nozzle body, for example, with a nozzle body having a different tip diameter / droplet formation size. Another advantage is that the fraction collection unit can be made of conventional, sturdy polyetheretherketone (PEEK) tubing, rather than the fragile fused silica tubing that is typically used in conventional systems.

[0031] In one example embodiment, the outer diameter of the tip of the nozzle assembly is 0.4 mm, the channel has an inner diameter of 0.3 mm, and the total volume is 1 μl. In another example embodiment, the outer diameter of the tip of the nozzle assembly is 0.4 mm, the fluid channel is divided into two parts, the first part of the fluid channel has an inner diameter of 0.3 mm, and the second part has an inner diameter of 0.5 mm, and the total volume of the fluid channel is 1.6 μl.

[0032] Typically, nozzles are designed with different nozzle bodies to fit into the receiving recesses of different fraction collection units.

[0033] The following briefly describes the problems / challenges addressed by the present disclosure. To obtain small droplets from a droplet generator / nozzle, the outer diameter of the droplet generator / nozzle tip must be relatively small. In one example using water at room temperature, the droplet size, expressed in μl, is approximately 15-20 times the outer diameter of the droplet generator / nozzle tip, expressed in mm. To achieve droplets with a size less than 10 μl, the outer diameter of the droplet generator / nozzle tip must be less than 0.5 mm. In conventional systems, droplets are typically formed by the end of the tubing itself, i.e., the conduit / tubing that fluidly couples the fluid source to the fraction collection unit, requiring the tubing to have an outer diameter less than 0.5 mm. At this size, the only readily available tubing is fused silica, which has numerous drawbacks, including being very fragile, requiring specialized cutting tools, and being relatively expensive.

[0034] As mentioned above, use of the nozzle assembly of the present disclosure with a conduit adapter configured for larger outer diameter conduits / tubing, such as standard PEEK 1 / 16" (1.59 mm), allows for easy access to such tubing, which is normally used in fluid sources and fraction collection units.

[0035] Technical and commercial advantages associated with these novel and unique features of the present disclosure include that it is robust and easy to use, its small droplet size and low internal volume result in low levels of peak broadening, and it can be produced relatively inexpensively.

[0036] 1 illustrates one 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 100, which may include select bioprocessing units such as a reservoir 151, a column 141, a detector 131, and a fraction collection unit 120. The bioprocessing system 100 in the form of a chromatography device 100 is described in more detail below.

[0037] The chromatography device 100 typically includes at least one inlet 155. Optionally, the inlet may be coupled to one or more reservoirs 151 configured to hold a fluid. It is understood that the chromatography device 100 may include any number of reservoirs and corresponding inlets. For example, the inlet 155 may be embodied as a tubular element such as a tube or hose. The chromatography device 100 may further include a controllable flow path unit (pump and valve) 102 and a column 141 including fluid ports 130-150. The column 141 may be included within the chromatography device or located external to the chromatography device.

[0038] The chromatography device 100 may further include a control unit 110 comprising circuitry such as a processor and memory. The memory may comprise instructions executable by the processor to operate the chromatography device to perform any of the steps and methods described herein, such as to direct the fraction collection unit 120 to the various receptacles 121-123.

[0039] Optionally, the chromatography device 100 may further comprise a fraction collection unit 120. The chromatography device 100 is further fluidly coupled to the fraction collection unit 120, thus enabling the partitioning of the sample into various containers, typically by a droplet former or nozzle assembly as disclosed herein.

[0040] It is noted that the present disclosure can be used with any application of the fraction collection unit 120 and is not limited to chromatography.

[0041] 2A shows an isometric view of a conduit adapter 210 of a nozzle assembly 200 in accordance with one or more embodiments of the present disclosure. In one embodiment, the conduit adapter 210 comprises a conduit interface portion 211 and / or a grip part 212 and / or a body interface portion 213.

[0042] Typically, the conduit interface portion 211 is configured to mechanically couple to the conduit and also fluidly couple to the conduit, thereby allowing fluid to flow from the fluid source to the nozzle assembly. In one example, the conduit interface portion 211 is formed with an outer diameter that is slightly larger than the inner diameter of the conduit, allowing the conduit to be mechanically coupled by frictional forces when threaded onto the conduit interface portion 211, and simultaneously fluidly coupled when the conduit and the inlet of the conduit interface portion 211 form a fluid channel.

[0043] In one example, the distal end of conduit interface portion 211 is shaped like a conduit, with an outer diameter of 7.5 mm, an inner diameter of 7.1 mm, and a height of 4 mm.

[0044] Typically, grip part 212 is configured to allow for a safe and secure grip of conduit adapter 210 when held by a user, for example, when the user threads a conduit from a fluid source onto conduit interface portion 211.

[0045] In one example, the grip part 212 is shaped as a ribbed cylinder having an outer diameter of 10.6 mm and a height of 8 mm.

[0046] Typically, body interface portion 213 is configured to form a fluid channel and / or to be removably attached to nozzle body 220 of nozzle assembly 200. Optionally, body interface portion 213 may further include an attachment element 216, such as, for example, a thread, configured to be removably attached to nozzle body 220 of nozzle assembly 200.

[0047] 2B shows a front view of the conduit adapter 210 of the nozzle assembly 200 in accordance with one or more embodiments of the present disclosure. Cross section AA is taken through the central axis of the conduit adapter 210.

[0048] 2C shows a cross-sectional view of the conduit adapter 210 of the nozzle assembly 200 in accordance with one or more embodiments of the present disclosure. The cross-section shown is taken along line AA as shown in FIG. 2B. As shown, a fluid channel 218 is formed from an inlet 219 in the conduit interface portion 211 to a distal end 213 of the conduit interface portion 211. Optionally, the body interface portion 213 further includes an attachment element 216, such as a thread, configured to be removably attached to a nozzle body 220 of the nozzle assembly 200.

[0049] In one example, body interface portion 213 has an overall height / length of 18.5 millimeters, and mounting element 216 has an overall height / length of 8 millimeters and is equipped with UNF 10-32 2A threads. Fluid channel 218 formed from inlet 219 to tip 213 has an inner diameter of 1.7 millimeters. Inlet 219 is shaped like a cone with a diameter of 4.5 millimeters at the tip and a diameter of 1.7 millimeters where it couples to fluid channel 218.

[0050] 3A shows an isometric view of a nozzle body 220 of a nozzle assembly 200 according to one or more embodiments of the present disclosure. In one embodiment, the nozzle assembly 200 comprises a nozzle portion 221 and an interface portion 222.

[0051] In another embodiment, the nozzle part 221 comprises a tip part 223 and / or a cylindrical part 224 and / or a conical part 225, selected from among these.

[0052] In another embodiment, the interface portion 222 comprises a selection of a grip part 227 and a collector interface portion 229. Typically, the grip part 227 is configured to allow a safe and secure grip of the nozzle body 220 when held / handled by a user, for example when the user installs the nozzle body 220 in the fraction collection unit 120. Typically, the collector interface portion 229 is configured to mechanically couple to the fraction collection unit 120, for example by comprising a shape corresponding to a receiving compartment / recess of the fraction collection unit 120, such as a cylinder with a certain outer diameter.

[0053] 3B shows a front view of nozzle body 220 of nozzle assembly 200 in accordance with one or more embodiments of the present disclosure. In one embodiment, nozzle assembly 200 comprises a nozzle portion 221 and an interface portion 222. Cross section AA is taken along the midline of nozzle body 220.

[0054] Figure 3C shows a cross-sectional view of nozzle body 220 of nozzle assembly 200 in accordance with one or more embodiments of the present disclosure. The cross-section shown is AA as shown in Figure 3B. In one embodiment, nozzle body 220 comprises a cavity or bore 2281 having a corresponding shape to body interface portion 213 of conduit adapter 210, and a fluid channel 2282 fluidly coupling the cavity to the tip of nozzle portion 221. In one embodiment, optionally, cavity or bore 2281 further comprises an attachment element 226, such as, for example, a thread, configured for removably attaching to conduit adapter 210 of nozzle assembly 200.

[0055] In one example, the overall height / total length of the nozzle body 220 is 29.4 mm. The overall height / total length of the collector interface portion 229 is 14.1 mm. The overall height / total length of the nozzle portion 221 is 68.9 mm. The overall height / total length of the grip part 227 is 6.4 mm. The inner diameter of the fluid channel 2282 is 0.298 mm at the narrow portion of the fluid channel and 0.5 mm at the wide portion.

[0056] 4 shows nozzle assembly 200 when conduit adapter 210 is attached to nozzle body 220 according to one or more embodiments of the present disclosure, where a fluid channel is formed from inlet 219 of conduit adapter 210 to tip 223 of nozzle portion 221.

[0057] In one embodiment, a nozzle assembly 200 is provided for a fraction collection unit 120 configured to collect one or more fluid samples. The nozzle assembly 200 includes a conduit adapter 210 configured to fluidly couple to a conduit. The conduit adapter 210 is further described in relation to Figures 2A-2C. In this embodiment, the nozzle assembly 200 further includes a nozzle body 220, optionally configured to be removably attached to the conduit adapter. The nozzle body 220 is further described in relation to Figures 3A-3C. In this embodiment, the nozzle body includes at least one nozzle portion 221 configured to eject droplets of one or more collected fluid samples at a tip 223 of the nozzle portion 221 and an interface portion 222 configured to mechanically couple the assembly 200 to the fraction collection unit. The mechanical coupling may include, for example, the nozzle body being at least partially received by a recess in the fraction collection unit 120. In this embodiment, the assembly forms a fluid channel from the inlet 219 of the conduit adapter 210 to the tip 223 of the nozzle portion 221 when the conduit adapter 210 is attached to the nozzle body 220 .

[0058] In one example, a user may connect a conduit or tube to the conduit adapter 210 by threading the conduit or tube onto the tubular conduit interface portion 211. The user may then place the nozzle body 220 or the collector interface portion 229 of the nozzle body 220 into the recess of the fraction collection unit 120. The user may then attach the conduit adapter 210 to the nozzle body 220 by inserting the body interface portion 213 into the cavity or bore 2281 and engaging the attachment elements 216, 226, for example, by rotating the conduit adapter 210 to engage mating threads.

[0059] In one embodiment, the outer diameter of the tip portion 223 of the nozzle portion 221 is in the range of 0.2 to 2 mm, and more preferably in the range of 0.3 to 0.5 mm.

[0060] In one embodiment, the inner diameter of the tip portion 223 of the nozzle portion 221 is preferably within a range of 0.1 to 1 mm, and more preferably within a range of 0.2 to 0.4 mm.

[0061] In one embodiment, the nozzle portion 221 comprises a cylindrical part 224 and a conical part 225 that comprises the tip of the nozzle portion.

[0062] In one embodiment, interface portion 222 further comprises a grip element 227 configured to provide a secure grip for a user to handle nozzle assembly 200 .

[0063] In one embodiment, the nozzle body and conduit adapter include attachment elements 216, 226 that are used to removably attach the nozzle body to the conduit adapter. In one example, the attachment elements 216, 226 are UNF 10-32 2B threads.

[0064] In one embodiment, the nozzle assembly 200 is made from plastic.

[0065] 5 illustrates the nozzle assembly 200 further comprising a locking element 510 in accordance with one or more embodiments of the present disclosure. In one embodiment, the interface portion 222 further comprises the locking element 510 configured to lock the nozzle assembly relative to the fraction collection unit 120. In one embodiment, the interface portion 222 further comprises a collector interface portion 229 configured to be received by a recess in the fraction collection unit 120, with the locking element 510 provided at one end of the collector interface portion 229 disposed adjacent to the nozzle portion 221. In one embodiment, the locking element 510 is formed in the shape of a flap extending from the collector interface portion 229 in a direction parallel to the midline of the nozzle body, with the flap comprising a locking lip at the end of the lip disposed furthest from the collector interface portion 229.

[0066] Finally, it is to be understood that the invention is not limited to the embodiments described above, but relates to and encompasses all embodiments that fall within the scope of the appended independent claims. [Explanation of symbols]

[0067] 100 Bioprocess system, chromatography device 102 Controllable flow path unit 110 control unit 120 Fraction Collection Unit 121 Container 130 fluid port 131 detector 141 Column 151 Reservoir 155 Entrance 200 Nozzle Assembly 210 Conduit Adapter 211 Conduit interface section 212 Grip Parts 213 Main body interface part, tip part 216 Mounting element 218 Fluid Channel 219 Entrance 220 Nozzle body 221 Nozzle part 222 Interface section 223 Tip 224 Cylindrical parts 225 Conical parts 226 Mounting elements 227 Grip parts, grip elements 229 Collector Interface Section 510 Locking Elements 2281 Boa 2282 Fluid Channel

Claims

1. 1. A nozzle assembly (200) for a fraction collection unit (120) configured to collect one or more fluid samples, comprising: a conduit adapter (210) configured to fluidly couple to a conduit; Nozzle body (220) and Equipped with The nozzle body (220) comprises at least a nozzle portion (221) configured to eject droplets of the one or more collected fluid samples at a tip (223) of the nozzle portion (221); an interface portion (222) configured to mechanically couple the nozzle assembly (200) to the fraction collection unit; Equipped with the nozzle assembly forms a fluid channel from an inlet (219) of the conduit adapter (210) to the tip (223) of the nozzle portion (221) when the conduit adapter (210) is attached to the nozzle body (220); the interface portion (222) further comprises a collector interface portion (229) configured to be received by a recess of the fraction collection unit (120); A nozzle assembly (200).

2. 2. The nozzle assembly (200) of claim 1, wherein the tip (223) of the nozzle portion (221) has an outer diameter within a range of 0.2 to 2 millimeters.

3. 3. The nozzle assembly (200) of claim 1 or 2, wherein the inner diameter of the tip (223) of the nozzle portion (221) is in the range of 0.1 to 1 millimeter in diameter.

4. 4. The nozzle assembly (200) according to any one of claims 1 to 3, wherein the nozzle portion (221) comprises a cylindrical part (224) and a conical part (225) that comprises the tip of the nozzle portion.

5. the interface portion (222) further comprises a locking element (510) configured to lock the nozzle assembly relative to the fraction collection unit; the locking element (510) is formed as a flap extending from the collector interface portion (229) in a direction parallel to the midline of the nozzle body; 5. The nozzle assembly (200) of any one of claims 1 to 4, wherein the flap comprises a locking lip at an end of the lip located furthest from the collector interface portion (229).

6. A nozzle assembly (200) as described in claim 5, wherein the locking element (510) is provided at one end of the collector interface portion (229) positioned adjacent to the nozzle portion (221).

7. 7. The nozzle assembly (200) of any one of claims 1 to 6, wherein the interface portion (222) further comprises a grip element (227) configured to enable a user to securely grip the nozzle assembly (200) for handling.

8. 8. The nozzle assembly (200) of any one of claims 1 to 7, wherein the nozzle body and the conduit adapter comprise attachment elements (216, 226) used to removably attach the nozzle body to the conduit adapter.

9. 9. The nozzle assembly (200) of any one of claims 1 to 8, wherein the nozzle assembly (200) is at least partially made from plastic.

10. 10. The nozzle assembly (200) of any one of claims 1 to 9, wherein at least one component of the nozzle assembly (200) comprises polyetheretherketone (PEEK).

11. 11. The nozzle assembly (200) of any one of claims 1 to 10, having a total internal volume of less than 10 μl.

12. 12. The nozzle assembly (200) of claim 11, wherein i) the outer diameter of the tip (223) of the nozzle portion (221) is about 0.4 mm, and the channel in the tip (223) has an inner diameter of about 0.3 mm and a total volume of about 1 μl, or ii) the outer diameter of the tip (223) of the nozzle portion (221) is about 0.4 mm, and the fluid channel in the tip (223) is divided into two parts, a first part having an inner diameter of about 0.3 mm and a second part having an inner diameter of about 0.5 mm, and a total volume of about 1.6 μl.

13. 13. The nozzle assembly (200) of any one of claims 1 to 12, wherein the nozzle body (220) is configured for removably attachment to the conduit adapter (210).

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