EP3984641A1 - Probenfläschchen und verfahren zur abgabe einer flüssigen probe an analysegeräte - Google Patents

Probenfläschchen und verfahren zur abgabe einer flüssigen probe an analysegeräte Download PDF

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Publication number
EP3984641A1
EP3984641A1 EP20306219.5A EP20306219A EP3984641A1 EP 3984641 A1 EP3984641 A1 EP 3984641A1 EP 20306219 A EP20306219 A EP 20306219A EP 3984641 A1 EP3984641 A1 EP 3984641A1
Authority
EP
European Patent Office
Prior art keywords
sample
sample vial
cavity
fluid
vial
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP20306219.5A
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English (en)
French (fr)
Inventor
Arkadiusz PAJAK
Sebastian Purmann
Jeffrey Steaffens
Neil Jones
Andrew GEDDES
Julien OUDIA
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sartorius Bioanalytical Instruments Inc
Original Assignee
Essen Instruments Inc
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Filing date
Publication date
Application filed by Essen Instruments Inc filed Critical Essen Instruments Inc
Priority to EP20306219.5A priority Critical patent/EP3984641A1/de
Publication of EP3984641A1 publication Critical patent/EP3984641A1/de
Withdrawn legal-status Critical Current

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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508Rigid containers without fluid transport within
    • B01L3/5085Rigid containers without fluid transport within for multiple samples, e.g. microtitration plates
    • B01L3/50853Rigid containers without fluid transport within for multiple samples, e.g. microtitration plates with covers or lids
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00Supporting devices; Holding devices
    • B01L9/06Test-tube stands; Test-tube holders
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00Supporting devices; Holding devices
    • B01L9/54Supports specially adapted for pipettes and burettes
    • B01L9/543Supports specially adapted for pipettes and burettes for disposable pipette tips, e.g. racks or cassettes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02Adapting objects or devices to another
    • B01L2200/025Align devices or objects to ensure defined positions relative to each other
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02Adapting objects or devices to another
    • B01L2200/026Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/12Specific details about manufacturing devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0832Geometry, shape and general structure cylindrical, tube shaped
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0848Specific forms of parts of containers
    • B01L2300/0851Bottom walls
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0848Specific forms of parts of containers
    • B01L2300/0858Side walls

Definitions

  • the invention relates to sample vials for delivery of micro fluid samples to analytical instruments for analysis, including delivery to flow cytometers and chromatographs.
  • a number of analytical instruments receive and process fluid samples with biological or chemical material to determine one or more properties of the biological or chemical material.
  • One analytical technique is flow cytometry, in which a flow of a fluid sample is evaluated in a flow cytometer for the presence of small particles, often of biological origin. A flow of the fluid sample passes through an investigation zone of the flow cytometer, where the fluid sample is subjected to a stimulus, normally light, and response to the stimulus is evaluated to provide information on particles in the fluid sample.
  • Traditional flow cytometry directed to evaluation of fluid samples for the presence of cells and other similarly-sized particles uses light scatter detection to identify passage of a particle through the investigation zone, and information about the specific compositional attributes of an identified particle may be obtained through the use of fluorescent stains known to stain certain biological features.
  • flow cytometry has limited applicability to evaluation of free, unassociated nanoparticles.
  • Light scatter detection becomes difficult as the particle size approaches the wavelength of the stimulating light source.
  • flow cytometers have been adapted for use to identify smaller biological particles in the nanoparticle size range, such as virions, virus-like particles, exosomes and other extracellular vesicles.
  • Some of these techniques have employed modified light scatter techniques to identify smaller size particles, while other techniques have relied entirely on a fluorescent emission response from one or more fluorescent stains targeted to biological features indicative of the particles of interest.
  • An example of a flow cytometer designed for detection and counting of virus-size particles through the use of only fluorescent stains is the Virus Counter ® 3100 flow cytometer (Sartorius Stedim Biotech).
  • Fluid samples are often provided in sample vials for feeding the fluid samples to a flow cytometer.
  • the sample vial interfaces with a sample feed probe, such as a needle, that is inserted into the sample vial and a volume of the fluid sample is withdrawn from the sample vial through the sample feed probe for delivery to the flow cytometer.
  • a sample feed probe such as a needle
  • Some flow cytometry applications require only a very small volume, for example less than a milliliter and often on the order of a few hundred to several hundred of microliters, and which may be referred to as micro samples.
  • Sample vials for providing such small sample volumes may be referred to as microvials or microsampling vials.
  • sample vials typically have a cylindrical body, with some common dimensions being 12 mm x 32 mm, 15 mm x 45 mm, 8 mm x 40 mm and 8 mm x 35 mm, with the first number being the cylindrical diameter of the vial and the second number being the height of the vial.
  • standardized cylindrical vial designs provide significant flexibility for use in a variety of situations, there are also significant limitations with respect to a number of processing situations.
  • fluid sample sizes can vary from a few hundred microliters, or smaller, to a milliliter, or more.
  • Some standardized cylindrical vials may provide a sufficient volume capacity to accommodate fluid samples over a significant range of micro sampling applications, but as required fluid sample volumes become smaller, a larger proportion of the sample volume tends to be lost to "dead volume" within the sample vial, which refers to a bottom portion of the sample vial from which fluid sample cannot be effectively removed by the sample feed probe. This is a significant problem with sample vials having a cylindrical container shape, which is exacerbated by many standard cylindrical vials that have a convex bottom.
  • a significant portion of a micro fluid sample may spread across the bottom of the cylinder and collect in cylinder corners and be effectively inaccessible to the sample feed probe.
  • the loss of a larger proportion of available fluid sample is costly, both in terms of lost biological sample material and in terms of lost reagents, such fluorescent stains.
  • Specially-designed sample vials and vial inserts into standard cylindrical vials have been available, which provide a narrower bottom profile of the fluid container to reduce dead volume at the bottom of the sample vial. But such specialty sample vials and vial inserts are more expensive and tend to be more difficult to manufacture, and in the case of vial inserts, are also more cumbersome and costly due to the added complexity and cost of the extra insert piece in addition to the standard cylindrical vial into which the insert is placed for use.
  • fluid sample is more often withdrawn from the sample vial by aspiration, such as through suction applied by a syringe
  • a fluid sample is withdrawn by pressurizing the sample vial to push fluid sample out of the sample vial and through the sample feed probe.
  • Sample vials made by injection molding from plastic materials tend to exhibit some level of pressure burst failure during use in pressurized feed applications. This problem may be avoided by the use of glass vials, but glass is significantly more expensive, and the use of glass presents other problems associated with potential breakage during handling.
  • each fluid sample is manually connected to a sample feed connector and manually disconnected following an analytical run. This may involve manually screwing each sample vial into place on the sample feed connector and then manually unscrewing the sample vial following completion of an analytical run. A new sample vial is then manually screwed into place for the next analytical run.
  • multiple fluid samples are automatically processed by an autosampler that is either integral with the analytical instrument or that interfaces with the analytical instrument to provide fluid samples for analysis.
  • multiple sample vials may be provided in an array, for example retained in an ordered pattern in a standardized processing tray, and a sample feed probe of the autosampler and the array of sample vials in the tray are indexed to permit the autosampler to access the different sample vials with the sample feed probe in an ordered sequence without manual intervention.
  • Standardized cylindrical vials are widely used in both manual attachment and autosampler situations, although such vials are not optimal especially for manual attachment handling.
  • the invention is directed to a sample vial for delivery of a fluid sample to an analytical instrument for analysis.
  • the sample vial is particularly useful to deliver very small fluid samples, such as smaller than 250 microliters, and even more particularly, such very small fluid samples that contain free, unassociated nanoparticles for analysis, for example by flow cytometry or chromatography.
  • nanoparticles may include, for example, a member selected from the group consisting of virions, virus-like particles and extracellular vesicles.
  • Such particles may be of a size with a maximum cross dimension (e.g., diameter) in a range of from 20 nanometers to 1 micron, whether or not labeled with one or more fluorescent stains.
  • Such particles may be referred to as being of virus size.
  • the sample vial has been designed especially for use in flow cytometry applications using fluid samples of very small volume and for evaluation of such unassociated nanoparticles, for example using the Virus Counter ® 3100 flow cytometer.
  • the sample vial is not limited to flow cytometry or evaluations for nanoparticles, and the sample vial may be used to deliver fluid samples to any analytical instrument with a fluid sample feed.
  • One other analytical technique for use with the sample vial is chromatography. There are many different variations of chromatography, but in general chromatography involves separation processing and investigation of properties of one or more separated parts prepared from an original fluid sample fed to a chromatograph to evaluate compositional attributes of the separated part or parts.
  • a first aspect of this disclosure is directed to a sample vial with particular design features.
  • the sample vial may comprise:
  • the sample vial provides a number of advantages.
  • the sample vial permits the processing of very small fluid samples, such as those noted above, without the cumbersome use of inserts into standard-sized cylindrical vials.
  • the sample vial is versatile for use with both pressurized systems that pressurize the sample vial to push fluid out of the sample vial for feed to an analytical instrument and non-pressurized systems that aspirate fluid out of the sample vial, such as by suction applied by a syringe.
  • the sample vial does not have a cylindrical exterior but rather has a ribbed exterior configuration that can be securely received in cylindrical receptacles and can be used in place of standard cylindrical vials.
  • the configuration of the sample vial provides for ease of manufacturability, and especially by injection molding, permitting the sample vial to be readily produced with different volume capacities for different application requirements.
  • the ribbed exterior portion of the sample vial facilitates secure gripping of the sample vial for manual attachment to and detachment from a sample feed connector of an analytical instrument, and also makes the sample vial less likely to roll away if the sample vial becomes disposed on its side on a smooth surface.
  • a second aspect of this disclosure is directed to an analytical sample delivery vessel.
  • the analytical sample delivery vessel may comprise a sample vial, preferably according to the first aspect, and a cap covering an open end of a fluid containment cavity in the sample vial.
  • a third aspect of this disclosure is directed to an array of sample vials with the array being beneficial, for example, for automated processing of a plurality of fluid samples for analysis by an analytical instrument.
  • the array of sample vials may comprise:
  • a fourth aspect of this disclosure is directed to a kit for handling a plurality of fluid samples for analytical evaluation.
  • the kit may comprise:
  • a fifth aspect of this disclosure is directed to an analytical system for analysis of one or more properties of a fluid sample.
  • the analytical system may comprise:
  • the material communication path may comprise a fluid communication path to communicate the fluid sample or a portion of the fluid sample from the sample feed probe to the investigation zone, either with or without intermediate processing to modify properties of the fluid sample (e.g., through reagent addition) or to separate out a part or parts of the fluid sample to be subjected to investigation in the investigation zone.
  • the material communication path may include a stationary phase of a chromatograph.
  • a sixth aspect of this disclosure is directed to a method for analyzing a fluid sample.
  • the method may comprise:
  • a seventh aspect of this disclosure is directed to a method of handling a plurality of fluid samples for analytical evaluation.
  • the method may comprise:
  • An eighth aspect of this disclosure is directed to a method for making a sample vial, preferably according to the first aspect.
  • the method may comprise molding, preferably by injection molding, the sample vial as a single-piece molded structure from a plastic material.
  • the sample vial in any of the second through eighth aspects is preferably the sample vial according to the first aspect.
  • the sample vial in any of the third through seventh aspects may be in an analytical sample delivery vessel of the second aspect.
  • the kit of the fourth aspect may provide components for assembly into the array of the third aspect, or components already assembled into the array of the third aspect.
  • the sample vial of the analytical system of the fifth aspect having the sample feed probe extending in the cavity thereof may or may not be in an array of the third aspect.
  • a method of the sixth aspect or the seventh aspect may include use of the array of the third aspect, the kit of the fourth aspect and/or the analytical system of the fifth aspect.
  • a sample vial 100 including an internal fluid containment cavity 102 to contain a fluid sample for delivery to an analytical instrument for analysis of one or more properties of material of the fluid sample, for example of unassociated nanoparticles in the fluid sample, which nanoparticles may or may not be stained with one or more fluorescent stains.
  • the cavity 102 is defined by a fluid containment wall 104.
  • the cavity 102 includes an open top adjacent a proximal end 106 of the sample vial 100 and a closed bottom disposed toward the distal end 108 of the sample vial 100.
  • the sample vial 100 has a longitudinal axis 110 extending in a longitudinal direction through the cavity 102, including through the open top and the closed bottom of the cavity 102.
  • the cavity 102 has a tapered portion 112 in which the cavity cross-section, transverse to (normal to) the longitudinal axis 110 and the longitudinal direction, tapers (reduces in size) in a direction toward the closed bottom of the cavity 102.
  • a cross-section being transverse to the longitudinal axis 110 (or the longitudinal direction) it is meant that the cross-section is in a plane that is transverse (normal) to the longitudinal axis 110.
  • a cross-section that is transverse to the longitudinal direction is also transverse to the longitudinal axis 110.
  • tapering it is meant that the area of the cavity cross-section, and preferably also a maximum cross dimension of the cavity cross-section (e.g., diameter of a circular cross-section), decreases in magnitude in the direction of the taper.
  • the cavity cross-section is circular at all longitudinal points along the longitudinal length of the cavity 102, and in the tapered portion 112 the diameter of the circular cross-section becomes smaller in the longitudinal direction moving from a proximal end to a distal end of the tapered portion 112.
  • first diameter D1 of the cavity cross-section at a first longitudinal position in the cavity 102 and a second, smaller diameter D2 at a second longitudinal position in the cavity 102 that is distal of the first longitudinal position.
  • the rate of taper of the cavity cross-section is larger near the top of the tapered section 112 and is smaller near the bottom of the tapered section 112.
  • the cavity 102 may have one of more longitudinal portions that are non-tapering (e.g., cylindrical), or may have no non-tapering longitudinal portions, even if some tapering portions may taper at a very small rate.
  • the top portions of the cavity 102 are shown in Figures 5 and 6 as non-tapered portions that are either cylindrical or that have only a minimal, very slight taper (e.g., angle of taper of less than 1°, or even less than 0.5°), which may be beneficial for mold removal in injection molding manufacture while not materially tapering the cavity cross-section.
  • the angle of taper refers to the angle of a wall of a tapering feature relative to the direction of taper of the feature.
  • the angle of taper of the tapered portion 112 of the cavity 102 refers to the angle of the surface of the fluid containment wall 104 exposed in the tapered portion 112 relative to the longitudinal axis.
  • the angle of taper will be a constant value over the length of the taper.
  • the angle of taper at any point will be based on the angle of a line tangent to the surface of the fluid containment wall 104 relative to the longitudinal axis 110.
  • a concave bottom portion 114 having a curved surface, a hemispherical surface in this example. As seen in Figures 5 and 6 , the curved surface of the concave bottom portion 114 is concave facing toward the open end of the cavity 102. As will be appreciated, the concave bottom portion 114 tapers very quickly to a nadir 116 of the cavity 102 disposed at a most distal point in the cavity 102 in the concave bottom portion 114.
  • the nadir 116 is at a lowest vertical elevation of the cavity 102 when the sample vial 100 is in a working orientation as it would normally be positioned for delivery of a fluid sample to an analytical instrument, with the proximal end 106 and the open end of the cavity 102 facing upward to receive from above a sample feed probe of an analytical instrument or of an autosampler that feeds fluid samples to an analytical instrument.
  • the configuration of the cavity 102 with a large cavity cross-section in a proximal portion of the cavity 102 near the open end and the relatively long tapered portion 112 transitioning to the very rapidly tapering concave bottom portion 114 permits efficient processing of very small volumes of fluid sample with little waste of fluid sample.
  • the narrowest point of the tapered portion 112 into which a sample feed probe (e.g., a needle) is to be inserted needs to only be slightly wider than the diameter of the sample feed probe, to permit effective flow of fluid sample around the sample feed probe to enter a fluid communication port adjacent a distal end of the sample fed probe.
  • the rapid narrowing in cross-section provided by the concave bottom portion 114 permits almost all fluid sample to be removed from the sample vial 100 without significant residual fluid sample being left behind.
  • the bottom of a sample feed probe may be inserted into the cavity 102 with the distal tip of the probe located at about the top of the concave bottom portion 114, or slightly above or slightly inside of the concave bottom portion 114, and the volume of the dead space for residual fluid sample that cannot be effectively removed may be similar to (equal to or slightly larger or smaller than) the volume in the concave bottom portion 114.
  • the minimum clearance fit between an external wall of the sample feed probe and the inside surface of the cavity 102 may be on the order of 3 millimeters or less, preferably no larger than 2.5 millimeters, more preferably no larger than 2 millimeters, or even no larger than 1.5 millimeters, but often at least 0.5 millimeter or at least 1 millimeter.
  • a standoff of a distal end of the sample feed probe from the nadir 116 is preferably very small, to limit the amount of residual fluid sample in dead space at the bottom of the cavity or that cannot be effectively withdrawn from the cavity 102.
  • Such a standoff from the nadir 116 may be, for example, no larger than 3 millimeters, no larger than 2.5 millimeters, no larger than 2 millimeters or no larger than 1.5 millimeters, although the standoff may often be at least 0.5 millimeter, preferably at least 0.7 millimeter and more preferably at least 1 millimeter.
  • One preferred range for the standoff is from 1.3 millimeters to 2 millimeters.
  • the maximum cross-dimension of the sample feed probe may be any convenient size (e.g., any convenient needle gauge) providing a desired rate of fluid withdrawal and being positionable in the vicinity of the concave bottom portion 114 to reasonably maximize access to a fluid sample for withdrawal and correspondingly minimize dead volume from which a portion of the fluid sample cannot be withdrawn.
  • the sample feed probe may have a maximum cross-dimension (e.g., outer diameter of needle) in the tapered portion 112 that is in a range of from 0.5 millimeter to 2.5 millimeters, which generally would include 25 gauge to 13 gauge hypodermic needle sizes, with a more preferred range having a lower limit of 0.7 millimeter, more preferably 1 millimeter and even more preferably 1.2 millimeters and an upper limit of 2.2 millimeters, more preferably 2.0 millimeters and even more preferably 1.8 millimeters.
  • a maximum cross-dimension e.g., outer diameter of needle
  • the dead volume in the sample vial 100 (the volume of fluid sample that cannot be effectively removed from the sample vial 100 through the sample feed probe) may be no greater than 50 microliters, preferably no greater than 25 microliters, and more preferably no greater than 15 microliters.
  • the dead volume may, however, often be at least 5 microliters.
  • the concave bottom portion 114 In addition to contributing to effective withdrawal of fluid sample from the cavity 102, the concave bottom portion 114 also provides for enhanced robustness of the sample vial 100 for use as a pressure vessel when used in applications in which the cavity 102 is pressurized to drive a fluid sample out of the cavity 102 and into a sample feed probe.
  • the concave bottom portion 114 is in the absence of sharp edge features, such as a bottom corner of a cylinder, that may tend to be more susceptible to higher residual internal stresses or molding imperfections that may increase potential for burst pressure failure points at such locations.
  • an injection molding gate entrance location 118 is positioned at the bottom of the fluid containment wall 104, corresponding with the concave bottom portion 114 of the cavity 102 including the nadir 116.
  • the molding gate entrance location 118 is a location where a molding gate introduces polymeric material into the mold cavity during injection molding to form the structure of the sample vial 100 as a single molded piece in the mold cavity. Such positioning of the injection molding gate entrance location 118 is conducive to even and uniform filling of a mold cavity with polymeric material during injection molding to form the longitudinally-oriented structure of the sample vial 100 as a single molded piece. Furthermore, providing some additional thickness of the fluid containment wall 104 at the location of the injection molding gate entrance location 118 advantageously promotes good distribution of polymer to fill the mold cavity during injection molding. The thicker wall feature at the molding gate entrance location 118 also provides additional protection against potential impairment of pressure containment performance that can result from molding imperfections that may develop in the vicinity of the molding gate entrance location 118.
  • the sample vial 100 includes a ribbed exterior portion 120, which also advantageously contributes both to versatility of the sample vial 100 for use in a variety of pressurized and non-pressurized applications and to enhancement of manufacturability of the sample vial 100 by injection molding.
  • the ribbed exterior portion 120 includes a plurality of longitudinally-extending exterior ribs 122, with the example sample vial 100 including a preferred embodiment four longitudinally-extending exterior ribs 122, for illustration purposes.
  • the ribbed exterior portion 120 also includes longitudinally-extending exterior recesses 124 between the ribs 122.
  • the recesses 124 generally correspond to the exterior surfaces of the fluid containment wall 104 between the ribs 122.
  • Each rib contains a terminal end face 126 facing radially outward relative to the longitudinal axis 110.
  • Each terminal end face 126 has a curved surface that curves about the longitudinal axis. In some preferred implementations the curved surface curves in an arc of a circle at all longitudinal positions, that is for all cross-sections transverse to the longitudinal direction.
  • the curved surfaces of the terminal end faces 126 may be curved surfaces of a cone (or frustrum of a cone), with the longitudinal axis being the axis of the cone of which the curved surfaces are a part.
  • the radial extent of the ribs 122 tapers slightly in the distal direction along the longitudinal length of the ribs, and the curved surfaces of the terminal end faces 126 are curved surfaces of a cone having an apex located distally beyond the distal end 108 of the sample vial 100.
  • Such a slight taper in the radial extent at the ribs 122 distally in the longitudinal direction may be advantageous for mold removal following injection molding during manufacture.
  • the curved surfaces of the terminal end faces 126 may be curved surfaces of a cylinder with a cylindrical radius from the longitudinal axis 110, and preferably the terminal end faces 126 of all of the ribs 122 have the same cylindrical radius from the longitudinal axis 110, such that the common cylindrical radius of the terminal end faces 126 defines a cylindrical envelope radius for the sample vial 100, advantageously permitting the sample vial 100 to be securely received in a cylindrical receptacle of close tolerance to the cylindrical envelope radius of the sample vial 100.
  • This provides versatility to the sample vial 100 as being compatible for receipt in standard processing trays designed for receipt of sample vials of cylindrical exterior shape.
  • the sample vial 100 may be securely received and processed in such a standard tray receptacle design, avoiding a need to use a non-standard receptacle design even through the sample vial 100 has a non-standard exterior configuration.
  • cylindrical envelope radius it is meant the radius of a minimum-size cylinder in which the sample vial 100 fits.
  • the cylindrical envelope radius may for example be the maximum radial extent of a proximal position of the ribs.
  • the degree of taper may typically be small, such as less than 1°, or even less than 0.5°.
  • the ribs 122 are longitudinally-extending, meaning that they extend in a direction away from the proximal end 106 and toward the distal end 108.
  • the ribs 122 extend in a straight line that is vertically, or nearly vertically, oriented when the sample vial 100 is in a working orientation.
  • the ribs may be in alternative configurations, for the ribs 122 may extend along slanted, curved or spiraling paths toward the distal end 108.
  • each rib 122 includes a radially-projecting fin 128 and a terminal flange 130 at a radial end of the fin 128.
  • the terminal flange 130 includes cantilevered flange portions extending laterally beyond the sides of the fin 128 and extending over portions of the recesses 124 adjacent to the fin 128.
  • the terminal end face 126 is on the outward (top) face of the terminal flange 130.
  • Each of the ribs 122 includes a distal extension portion 132 that extends in the longitudinal direction distally beyond a distal end of the fluid containment wall 104 at the bottom of the cavity 102, which corresponds with the exterior surface of the fluid containment wall 104 at the nadir 116.
  • the sample vial 100 when the sample vial 100 is standing on a flat surface in the working orientation, for example as shown in Figure 2 , the sample vial 100 is supported by the distal extension portions 132, with the molding gate entrance location 118 advantageously raised above the flat surface.
  • the distal extension portions 132 are distal extensions of the terminal flanges 130 in the example of the sample vial 100.
  • the depth of the exterior recesses 124, relative to the corresponding radial tops of the exterior ribs 122 on the terminal end faces 126, increases along the tapered portion in the longitudinal direction toward the closed bottom of the cavity 102, because the exterior configuration of the sample vial 100 in the recesses 124 tapers in a manner corresponding to the taper of the cavity cross-section in the tapered portion 112 of the cavity 102.
  • the height of the ribs 122, relative to the corresponding recesses increases in the longitudinal direction toward the closed bottom of the cavity 102.
  • Figure 8 illustrates this by showing a first depth H 1 of a recess 124 relative to a radial top of an adjacent rib 122 at a first longitudinal location and a second depth H 2 of the same recess 124 relative to the radial top of the same adjacent rib 122 at a more distal second longitudinal location toward the distal end 108 of the sample vial 100.
  • the outer radius of the sample vial 100 in the recesses 124 relative to the longitudinal axis 110 is tapering (reducing in size) in a corresponding manner to the taper of the cavity cross-section over the tapered portion 112.
  • This configuration permits the thickness of the fluid containment wall 104 in the recess areas 124 to be maintained at a constant, or relatively constant, thickness for most or all of the longitudinal length of the tapered portion 112 of the cavity 102, while also permitting the radial tops of the ribs 122 on the terminal end faces 126 to be maintained at a constant radial distance from the longitudinal axis 110.
  • the ribbed exterior configuration permits the longitudinal ends of the extension portions 132 to provide stable support for the sample vial 100 in the working orientation on a flat surface, for example a flat bottom surface of a tray receptacle or a flat surface of a work bench. Also, the ribbed exterior configuration permits the wall thickness of the fluid containment wall 104 to be kept small in the recesses 124, as the shape of the exterior surface of the fluid containment wall 104 may be made to correspond to the shape to the interior surface of the fluid containment wall 104 exposed in the cavity 102.
  • a thin wall thickness of the fluid containment wall 104 in the recesses 124 permits use of various polymeric materials of construction (e.g., polyolefin compositions, and preferably polypropylene compositions) while still providing reasonable optical transparency through the thin wall portions in the recesses 124 to permit visual observation of contents in the cavity 102 through the fluid containment wall 104.
  • a preferred material of construction is semi-crystalline polypropylene, such as polypropylene compositions including clarifying and/or nucleating agents to improve transparency.
  • the ribbed exterior portion 120 were instead configured as a cylinder with a cylindrical radius of an extent of the terminal end faces 126 of the ribs 122, because such a cylindrical configuration would not provide thin-walled portions for the fluid containment wall 104 as are provided in the recesses 124 of the configuration of the sample vial 100.
  • the ribbed exterior portion 120 is a more complex shape than a cylinder, the ribbed exterior portion enhances manufacturability by injection molding relative to a cylindrical, or non-cylindrical, configuration.
  • the geometric configuration of the ribbed exterior portion 120 permits the inclusion of the cavity 102 with tapering cavity cross-section while at the same time maintaining relatively uniform thicknesses for molded features around the cavity 102.
  • relatively uniform thicknesses may be used for all or most of the portions of fluid containment wall 104 exposed in the recess areas, for the fins 128 and for the terminal flanges 130, as opposed to the large differences in feature thicknesses that would result from a cylindrical exterior configuration as the fluid containment wall thickness would necessarily increase significantly over the tapered portion 112 of the cavity 102 as the cavity cross-section decreases toward the closed bottom of the cavity 102.
  • Having mold features mostly of a relatively uniform thickness is advantageous for good moldability during injection molding, as such features tend to fill in a relatively uniform manner and without development of undue pressures during mold filling operations.
  • the sample vial 100 may be made in the form of a single molded piece made with relatively thin molded features of relatively uniform thicknesses, such that no point in the molded structure is very far distant from an exposed surface (e.g., exterior surface of the sample vial 100 or surface of the fluid containment wall 104 exposed in the cavity 102). This is the case even with a somewhat enlarged thickness of the fluid containment wall 104 in the vicinity of the nadir 116 and the molding gate entrance location 118, as discussed elsewhere.
  • the longitudinally-extending ribs 122 advantageously function as flow leaders during injection molding, further promoting even distribution of polymer without development of undue pressures during mold filling operations.
  • the ribs 122 also advantageously provide for improved grip and leverage for rotation of the sample vial 100 by a user to grasp and rotatably engage the sample vial 100 with a threaded sample feed connector of an analytical instrument.
  • the spaced ribs 122 further provide a safety advantage of inhibiting rolling of the sample vial 100 on flat surfaces (e.g., work bench) if the sample vial 100 is either placed or falls onto its side.
  • the ribbed exterior configuration of the sample vial 100 also advantageously provides flexibility for use with a specially-designed tray, if desired, including specially-designed receptacles to receive the sample vials 100 and engage with features of the ribbed exterior portion 120, to permit enhanced processing options for the sample vials 100 in a tray.
  • each receptacle of the specially-designed tray may include a rotational stop feature that engages with one or more of the ribs 122 of a sample vial 100 received in the receptacle, thereby preventing the vial from being fully rotatable relative to the receptacle.
  • Such a rotational stop feature may include one or more engagement protrusions received between a pair of adjacent ribs 122 to prevent or limit an extent of rotation of the sample vial 100 received in the receptacle.
  • Such a complementary engagement between features of the sample vial 100 and a tray receptacle advantageously permits implementation of automated processing of the sample vials 100.
  • the sample vials 100 may be more securely engaged and retained in the specially-designed tray during processing by an autosampler to withdraw fluid samples from the sample vials 100.
  • the sample vials 100 received in such specially-designed receptacles may be subjected to automated processing that applies a rotational force to the sample vials 100.
  • sample vials 100 received in receptacles of a tray may be subjected to automated capping with threaded caps rotated by automated handling equipment to rotatably engage a cap with a corresponding threaded engagement structure of a sample vial 100 while the sample vial 100 is prevented by the rotational stop feature from rotating in the receptacles while the cap is being engaged with the sample vial 100.
  • the sample vial 100 includes an engagement portion 134 located longitudinally proximal of the ribbed exterior portion 120.
  • An exterior shoulder portion 138 is located longitudinally between the engagement portion 134 and the ribbed exterior portion 120 of the sample vial 100.
  • the shoulder portion 138 has a circumferentially continuous surface that expands out to the radial extent of the ribs 122 at a distal end of the shoulder portion 138.
  • the cylindrical envelope radius will typically correspond to a location or locations of a maximum cross dimension across the sample vial 100 transverse (normal) to the longitudinal axis 1110.
  • the cylindrical envelope radius of the sample vial 100 corresponds with a maximum radial extent of the ribs 122 at the curved surfaces of the terminal end faces 126, which in the example sample vial 100 also correspondent with a maximum radial extent of the shoulder portion 138 from which the ribs 122 extend in the longitudinal direction.
  • the engagement portion 134 has an engagement structure to engage a corresponding engagement structure of a cap to cover the cavity 102 or to engage a sample feed connector of an analytical instrument.
  • a cap may be designed for interaction with an autosampler (e.g., with a septum or a needle port to accept insertion of a sample feed probe).
  • the engagement structure 134 is a threaded structure for making a rotatable connection with a correspondingly threaded engagement structure of a cap or sample feed connector.
  • the engagement structure 134 could have a different configuration, for example for a snap, crimp or clamp securement with a corresponding engagement structure, for example to accept a snap-fit or crimped cap or for clamp securement to a sample feed connector.
  • the sample vial 100 includes an enhancement in the engagement structure 134 at the proximal end 106, where the top of the engagement structure 134 includes a circular sealing lip 136 with a rounded exterior edge profile circumferentially around the longitudinal axis 110, for example to engage and compress a gasket feature of a corresponding engagement structure and to form a fluid seal without contacting the gasket feature with a sharp edge structure of the sample vial 100.
  • the rounded edge profile of the sealing lip 136 is best seen in the partial cross-section of the engagement structure 134 shown in Figure 7 .
  • sample vial of the disclosure may include various dimensions, materials of construction and other features of the sample vial 100 as described in the numbered paragraphs of the Additional Implementation Examples provided below.
  • Figure 9 shows an analytical sample delivery vessel 140 including the example sample vial 100 and a cap 142 engaged with the engagement portion 134 to secure the cap 142 to the sample vial 100 to cover the open end of the cavity 102 of the sample vial 100.
  • the cap 142 includes a port 144 for receipt of a sample feed probe through the cap and into the cavity 102 for removal of a fluid sample for analysis by an analytical instrument.
  • the port 144 may include a septum that is pierceable by the sample feed probe to access the cavity 102 and/or may include a sealing feature, such as on O-ring, to seal around the sample feed probe, for example to facilitate pressurization of the cavity 102.
  • the cap 142 may include a gasket feature inside the cap adjacent the top, and which is compressed by the sealing lip 136 of the sample vial 100 to form a fluid seal between the sample vial 100 and the cap 142.
  • Figure 10 shows an array 200 of sample vials, such as may be used for automated processing by an autosampler or other automated processing equipment.
  • the array 200 includes a plurality of sample vials illustrated as the example sample vials 100 of Figures 1-8 , for convenience of description.
  • the sample vials 100 are illustrated as capped with caps 142, in the form of the example analytical sample delivery vessel 140 shown in Figure 9 .
  • the array 200 includes a tray 202 having a plurality of receptacles 204 configured to receive the plurality of sample vials 100.
  • the receptacles may generally have a circular cross-section with a diameter to receive a cylindrical envelope of the sample vial 100, for example as defined by the maximum radial extent of a sample vial 100 from the longitudinal axis 110 (e.g., occurring at a maximum radial extent of the ribs 122 and/or the shoulder portion 138).
  • the receptacles 204 may include a rotational stop feature with one or more engagement protrusions to engage and limit or prevent rotation of the received sample vial 100 relative to the tray 202 and relative to the corresponding receptacle 204 in which the sample vial 100 is received.
  • a clearance fit between a sample vial 100 and a receptable 204 may provide a relatively snug fit for stability and good alignment for interaction with an autosampler.
  • the clearance fit may be the difference between a cylindrical envelope diameter of the sample vial 100, or of the portion of the sample vial 100 received in the receptacle 204, and the cylinder diameter of a cylindrically shaped receptable 204 or may be the difference between such a cylindrical envelope diameter and a square side dimension when the receptacle is configured with a square-shaped receiving geometry.
  • Figure 11 illustrates the tray 202 of Figure 10 with one example of a configuration for a rotational stop feature including four protrusions 206 projecting radially inward from the wall of the receptacle 204.
  • the protrusions 206 are radially spaced to correspond with the radial spacing of the recesses 124 of the sample vial 100, and the protrusions 206 have a width and projection length into the receptacle 204 so that the protrusions 206 are received in the recesses 124 when the sample vial is properly received in the receptacle 204, to thus limit or prevent rotation of the sample vial 100 relative to the tray 202 and relative to the receptacle 204 in which the sample vial 100 is received.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Sampling And Sample Adjustment (AREA)
EP20306219.5A 2020-10-16 2020-10-16 Probenfläschchen und verfahren zur abgabe einer flüssigen probe an analysegeräte Withdrawn EP3984641A1 (de)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100120133A1 (en) * 2008-10-31 2010-05-13 Biomerieux, Inc. Separation device for use in the separation, characterization and/or identification of microorganisms
WO2010132829A2 (en) * 2009-05-15 2010-11-18 Biomerieux, Inc Combined detection instrument for culture specimen containers and instrument for identification and/or characterization of a microbial agent in a sample
US20140364296A1 (en) * 2012-01-31 2014-12-11 Argos Therapeutics, Inc. Centrifuge vessels suitable for live cell processing and associated systems and methods
US20190366328A1 (en) * 2017-01-25 2019-12-05 Yantai Ausbio Laboratories Co., Ltd. Equipment and methods for automated sample processing for diagnostic purposes

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100120133A1 (en) * 2008-10-31 2010-05-13 Biomerieux, Inc. Separation device for use in the separation, characterization and/or identification of microorganisms
WO2010132829A2 (en) * 2009-05-15 2010-11-18 Biomerieux, Inc Combined detection instrument for culture specimen containers and instrument for identification and/or characterization of a microbial agent in a sample
US20140364296A1 (en) * 2012-01-31 2014-12-11 Argos Therapeutics, Inc. Centrifuge vessels suitable for live cell processing and associated systems and methods
US20190366328A1 (en) * 2017-01-25 2019-12-05 Yantai Ausbio Laboratories Co., Ltd. Equipment and methods for automated sample processing for diagnostic purposes

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