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. However, traditional 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. More recently, 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with a sample feed probe, such as a needle, that is inserted into the sample vial and a volume of the fluid sample is withdrawn from the sample vial through the sample feed probe for delivery to the flow cytometer. 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. There has been a trend toward standardization of sample vial dimensions to provide flexibility to interface with a number of different analytical instruments and for different analytical situations. Such sample vials typically have a cylindrical body, with some common dimensions being 12 mm×32 mm, 15 mm×45 mm, 8 mm×40 mm and 8 mm×35 mm, with the first number being the cylindrical diameter of the vial and the second number being the height of the vial. Although such 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.
In micro sample applications, 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.
Also, although fluid sample is more often withdrawn from the sample vial by aspiration, such as through suction applied by a syringe, in some applications 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.
Additionally, some analytical situations involve single sample processing in which 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. In other analytical situations, 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. In an autosampler situation, 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.
There remains a significant need for versatile, low-cost sample vials with flexibility for enhanced performance over a variety of different analytical processing situations.
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. Such 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. However, 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. For example, 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.
Several other feature refinements and additional features are applicable to each of these and other aspects of this disclosure. These feature refinements and additional features may be used individually or in any combination within the subject matter of this aspect or any other aspect of this disclosure. As such, each of the following features may be, but is not required to be, used with any other feature or a combination of features of this aspect or any other aspect of this disclosure.
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.
Numerous additional features and advantages of the present disclosure will become apparent to those skilled in the art upon consideration of the further description provided hereinbelow and in the drawings.
With reference to
As shown in
At the bottom of the cavity 102 is a concave bottom portion 114 having a curved surface, a hemispherical surface in this example. As seen in
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. The robustness for use in pressurized applications is further enhanced by providing a somewhat larger minimum wall thickness of the fluid containment wall 104 about the concave bottom portion 114, relative to the minimum wall thickness of the fluid containment wall 104 along the length of the tapered portion 112 of the cavity 102, as seen best in
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. When a radial extent of the ribs 122 tapers in 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. In some implementations 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. When the radial extent of the ribs 122 is at a uniform distance from the longitudinal axis 110, 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. By cylindrical envelope radius, it is meant the radius of a minimum-size cylinder in which the sample vial 100 fits. When the radial distance of the curved surface of the terminal end faces 126 taper in a distal direction on the ribs (e.g., curved surfaces of a cone) the cylindrical envelope radius may for example be the maximum radial extent of a proximal position of the ribs. When the radial distance of the curved surfaces of the terminal end faces 126 tapers in a distal direction (e.g., curved surfaces of a cone), the degree of taper may typically be small, such as less than 1°, or even less than 0.5°.
As noted, 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. In the example sample vial 100, 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. In other variations, the ribs may be in alternative configurations, for the ribs 122 may extend along slanted, curved or spiraling paths toward the distal end 108.
As shown in
In the example 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. Stated in an alternative manner, the height of the ribs 122, relative to the corresponding recesses, increases in the longitudinal direction toward the closed bottom of the cavity 102.
Several advantages are provided by the ribbed exterior configuration. One advantage is that the longitudinal ends of the extension portions 132 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. As the sample vial 100 will typically be made of a molded plastic material by injection molding, 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. Some other example materials of construction are identified below. The same level of transparency would not be available if 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.
Also, even though 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. As seen in
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. For example, 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. For example, 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. As another example, 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. In that regard, the 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. As seen in
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. Such 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). In the illustrated example sample vial 100, 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. Alternatively, 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
The sample vial of the disclosure, including the example sample vial 100 of
Reference is now made to
Reference is now made to
An example base configuration for use with the sample vial is summarized in the following numbered paragraph 1:
1. A sample vial for delivery of a fluid sample to an analytical instrument for analysis, comprising:
Some other contemplated example combinations for use with the sample vial including the example base configuration of numbered paragraph 1 above, with or without additional features as disclosed above or elsewhere herein, are summarized in the further numbered paragraphs presented below:
2. The sample vial of paragraph 1, wherein the cavity comprises a concave bottom portion including the nadir.
3. The sample vial of paragraph 2, wherein the concave bottom portion is defined by a curved surface of a sphere.
4. The sample vial of paragraph 3, wherein the curved surface of a sphere has a radius in a range of from having a lower limit of 0.8 millimeter, 1 millimeter, 1.3 millimeters or 1.5 millimeters and an upper limit of 2.5 millimeters, 2 millimeters, 1.8 millimeters or 1.7 millimeters.
5. The sample vial of any one of either one of paragraph 3 or paragraph 4, wherein the curved surface of a sphere comprises a hemisphere.
6. The sample vial of any one of paragraphs 2-5, wherein the longitudinal axis passes through the concave bottom portion, and optionally through the nadir.
7. The sample vial of any one of paragraphs 2-6, wherein the concave bottom portion tapers in a downward direction along the longitudinal axis from a maximum cross dimension of at least 1.5 millimeters and preferably at least 2 millimeters, and in either case preferably not greater than 6 millimeters and more preferably not greater than 4 millimeters, to the nadir over a distance in the longitudinal direction in a range of from 0.5 millimeter to 3 millimeters and preferably in a range of from 0.5 millimeter to 2 millimeters.
8. The sample vial of any one of paragraphs 1-6, wherein the fluid containment wall at the nadir has a wall thickness that is larger than a minimum wall thickness of the fluid containment wall over the tapered portion of the cavity.
9. The sample vial of paragraph 8, wherein the wall thickness at the nadir is a multiple of the minimum wall thickness over the tapered portion of the cavity of at least 1.1, at least 1.3, at least 1.4 or at least 1.5, and such multiple may optionally be no larger than 3, no larger than 2.5, no larger than 2 or no larger than 1.8.
10. The sample vial of any one of paragraphs 1-9, wherein a minimum wall thickness over the tapered portion of the cavity is at least 0.5 millimeter, at least 0.8 millimeter, at least 0.9 millimeter or at least 1 millimeter, and optionally no larger than 2.5 millimeters, no larger than 2 millimeters, no larger than 1.5 millimeters or no larger than 1.3 millimeters.
11. The sample vial of any one of paragraphs 1-10, wherein fluid containment wall includes a molding gate entrance location.
12. The sample vial of paragraph 11, wherein the molding gate entrance location includes the fluid containment wall at the nadir.
13. The sample vial of any one of paragraphs 1-12, wherein:
14. The sample vial of any one of paragraphs 1-13, wherein the ribbed exterior portion comprises a longitudinal portion circumferentially surrounding a corresponding longitudinal portion of the tapered portion of the cavity, wherein on the longitudinal portion of the ribbed exterior portion a depth of the exterior recess relative to adjacent said ribs increases in a longitudinal direction toward the distal end of the sample vial.
15. The sample vial of paragraph 14, wherein the longitudinal portion of the ribbed exterior portion, and the corresponding longitudinal portion of the tapered portion of the cavity, has a longitudinal length in the longitudinal direction in a range having a lower limit of 6 millimeters, 8 millimeters, 10 millimeters or 14 millimeters and an upper limit of 45 millimeters, 35 millimeters, 30 millimeters or 25 millimeters.
16. The sample vial of either one of paragraph 14 or paragraph 15, wherein the depth of the exterior recesses increases, and preferably continuously increases, in the longitudinal direction toward the distal end of the sample vial along the longitudinal portion of the ribbed exterior portion, and optionally the depth increases by at least 0.5 millimeter, preferably at least 0.8 millimeter, more preferably at least 1 millimeter and even more preferably at least 1.2 millimeters over the longitudinal portion of the ribbed exterior portion.
17. The sample vial of any one of paragraphs 16, wherein the increase in the depth of the exterior recesses along the longitudinal portion of the ribbed exterior portion is from a first depth of no greater than 2.2 millimeters to a larger second depth including the increase in the depth.
18. The sample vial of any one of paragraphs 14-17, wherein:
19. The sample vial of any one of paragraphs 1-18, wherein each said rib comprises a radially terminal end face with a curved surface curving about the longitudinal axis, optionally the curved surface is selected from the curved surface of a cylinder and a curved surface of a cone, wherein in the case of a curved surface of a cylinder the cylinder optionally having a cylindrical radius from the longitudinal axis, and wherein in the case of a curved surface of a cone the cone having a central axis coincident with the longitudinal axis.
20. The sample vial of any one of paragraphs 1-19, wherein the radially terminal end faces of adjacent said ribs are separated by a distance of at least 2 millimeters, at least 3 millimeters or at least 4 millimeters, and optionally the distance is not greater than 12 millimeters, not great than 10 millimeters or not greater than 8 millimeters.
21. The sample vial of any one of paragraphs 1-20, wherein the ribs are equally spaced radially about the longitudinal axis.
22. The sample vial of any one of paragraphs 1-21, comprising from 3 to 6 of the ribs.
23. The sample vial of any one of paragraphs 1-22, comprising 4 of the ribs.
24. The sample vial of any one of paragraphs 1-23, wherein each said rib comprises a radially-projecting fin.
25. The sample vial of paragraph 24, wherein each said rib comprises a terminal flange on a radial end of the fin, wherein the terminal flange includes cantilevered flange portions extending laterally beyond the sides of the fin and over portions of the exterior recesses.
26. The sample vial of paragraph 25, wherein the terminal flange has a width laterally across the terminal flange in a direction transverse to the longitudinal direction in a range of from 1.5 millimeters to 6 millimeters.
27. The sample vial of either one of paragraph 25 or paragraph 26, wherein an outward face of the terminal flange comprises a said radially terminal end face with the curved surface according to paragraph 19.
28. The sample vial of paragraph 19 or 27, wherein each said curved surface extends from 5° to 60° radially about the longitudinal axis.
29. The sample vial of any one of paragraphs 19, 27 and 28, comprising a cylindrical envelope radius equal to a maximum radial distance from the longitudinal axis to a said curved surface.
30. The sample vial of any one of paragraphs 27-29, wherein the maximum radial distance is in a range having a lower limit of 3.5 millimeters or, preferably, 5 millimeters and an upper limit of 8 millimeters or, preferably, 6 millimeters.
31. The sample vial of any one of paragraphs 1-30, wherein each point in a molded plastic feature of the sample vial is not greater than 1.8 millimeters, preferably not greater than 1.5 millimeters, more preferably not greater than 1.2 millimeters and even more preferably not greater than 1 millimeter, distant from an exposed surface of the sample vial.
32. The sample vial of any one of paragraphs 1-31, wherein the ribbed exterior portion has a longitudinal length in the longitudinal direction in a range of having a lower limit of 10 millimeters, 15 millimeters, 18 millimeters or 20 millimeters and an upper limit of 45 millimeters, 35 millimeters, 30 millimeters or 25 millimeters.
33. The sample vial of any one of paragraphs 1-32, wherein the sample vial has a longitudinal length in the longitudinal direction in a range having a lower limit of 25 millimeters, 30 millimeters or 32 millimeters and an upper limit of 50 millimeters, 40 millimeters or 35 millimeters.
34. The sample vial of any one of paragraphs 1-33, wherein the sample vial has a cylindrical envelope radius from the longitudinal axis in a range having a lower limit of 3.5 millimeters or, preferably, 5 millimeters and an upper limit of 8 millimeters or, preferably, 6 millimeters.
35. The sample vial of any one of paragraphs 1-34, wherein the tapered portion of the cavity has a longitudinal length in the longitudinal direction in a range having a lower limit of 5 millimeters, 10 millimeters or 15 millimeters to and an upper limit of 49 millimeters, 39 millimeters or 31 millimeters, with one preferred range being from 10 millimeters to 31 millimeters.
36. The sample vial of any one of paragraphs 1-35, wherein the cavity comprises a non-tapered portion located longitudinally proximal of the tapered portion, the non-tapered portion having no taper or a small taper with an angle of taper not exceeding 1°, or even not exceeding 0.5°, such as to facilitate enhanced mold separation following molding relative to having not even a small taper.
37. The sample vial of paragraph 36, wherein the non-tapered portion of the cavity has a longitudinal length in the longitudinal direction in a range of from 5 millimeters having a lower limit of 4 millimeters, 8 millimeters or 12 millimeters and an upper limit of 40 millimeters, 30 millimeters or 20 millimeters.
38. The sample vial of any one of paragraphs 1-37, wherein the tapered portion of the cavity comprises a fluid containment volume in a range having a lower limit of 20 percent, 30 percent or 35 percent and an upper limit of 100 percent, 75 percent or 50 percent of a total fluid containment volume of the cavity.
39. The sample vial of any one of paragraphs 1-38, wherein the tapered portion of the cavity has a longitudinal length in the longitudinal direction in a range having a lower limit of 25 percent, 35 percent or 45 percent and an upper limit of 100 percent, 80 percent or 50 percent of a total longitudinal length of the cavity in the longitudinal direction.
40. The sample vial of any one of paragraphs 1-39, wherein the cavity has a longitudinal length in the longitudinal direction in a range having a lower limit of 20 millimeters, 25 millimeters, or 29 millimeters and an upper limit of 49 millimeters, 39 millimeters or 34 millimeters.
41. The sample vial of any one of paragraphs 1-40, wherein the cavity has a total fluid containment volume in a range having a lower limit of 200 microliters, 350 microliters or 500 microliters and an upper limit of 1.5 milliliters, 1 milliliter or 750 microliters.
42. The sample vial of any one of paragraphs 1-41, comprising an engagement portion located longitudinally proximal of the ribbed exterior portion, the engagement portion comprising an engagement structure to engage a corresponding engagement structure of a member selected from the group consisting of a cap and a sample feed connector of an analytical instrument.
43. The sample vial of paragraph 42, wherein the engagement structure comprises threads to rotatably engage corresponding threads of the corresponding engagement structure.
44. The sample vial of either one of paragraph 42 or paragraph 43, wherein the engagement portion has a cylindrical envelope radius from the longitudinal axis that is smaller than a cylindrical envelope radius of the ribbed exterior portion.
45. The sample vial of any one of paragraphs 42-44, wherein the engagement structure comprises a circular sealing lip with a rounded exterior edge profile circumferentially around the longitudinal axis at the proximal end of the sample vial, to engage and compress a gasket feature of the corresponding engagement structure to form a fluid seal without contacting the gasket feature with a sharp edge structure of the sample vial.
46. The sample vial of any one of paragraphs 42-45, comprising an exterior shoulder portion positioned longitudinally between the engagement portion and the ribbed exterior portion, wherein the shoulder portion has a cylindrical envelope radius from the longitudinal axis that is larger than a cylindrical envelope radius from the longitudinal axis of the engagement portion.
47. The sample vial of paragraph 46, wherein the exterior shoulder portion has a continuous surface circumferentially around the longitudinal axis.
48. The sample vial of either one of paragraph 46 or paragraph 47, wherein the exterior shoulder portion has a cylindrical envelope radius from the longitudinal axis of no larger than, and optionally equal to, a cylindrical envelope radius of the exterior ribbed portion from the longitudinal axis.
49. The sample vial of any one of paragraphs 1-48, wherein the cavity cross-section is circular at all points along the longitudinal axis.
50. The sample vial of any one of paragraphs 1-49, wherein the cavity has a maximum cross dimension transverse to the longitudinal direction in a range having a lower limit of 3 millimeters, 4 millimeters or 5 millimeters and an upper limit of 14 millimeters, 10 millimeters and 7 millimeters.
51. The sample vial of any one of paragraphs 1-50, wherein the cavity has a longitudinal section extending over a longitudinal distance of at least 3 millimeters, and preferably at least 5 millimeters in the longitudinal direction and having a maximum cross dimension transverse to the longitudinal direction of no larger than 5 millimeters, and preferably no larger than 4 millimeters and more preferably no larger than 3.5 millimeters, and a minimum cross-dimension transverse to the longitudinal direction of no smaller than 2 millimeters preferably no smaller than 2.5 millimeters and more preferably no smaller than 3 millimeters. Such a longitudinal section may be fully or partially within the tapered portion of the cavity, and may advantageously accommodate passage therethrough of a sample feed probe of an analytical instrument to provide annular space between the fluid containment wall and the exterior of the probe for flow of fluid sample around the probe and into a distal fluid entry port at a distal end of the probe during removal of sample fluid from the cavity for analysis, and with the annular space providing a flow restriction area to inhibit premature breakthrough of air into the fluid entry port.
52. The sample vial of paragraph 51, wherein the longitudinal section of the cavity has a distal end no more than 4 millimeters, preferably no more than 3 millimeters, more preferably no more than 2.5 millimeters, even more preferably no more than 2 millimeters and still more preferably no more than 1.8 millimeters, longitudinally proximal of the nadir in the longitudinal direction, and often no less than 0.1 millimeter, and preferably no less than 0.2 millimeter, longitudinally proximal of the nadir in the longitudinal direction.
53. The sample vial of either one of paragraph 51 or paragraph 52, wherein the longitudinal section is part of the tapered portion.
54. The sample vial of any one of paragraphs 1-53, wherein the fluid containment wall includes optically transparent portions in the exterior recesses to provide for visual observation of contents in the cavity through the fluid containment wall.
55. The sample vial of any one of paragraphs 1-54, in the form of a single-piece, injection molded plastic structure.
56. The sample vial of any one of paragraphs 1-55, wherein the sample vial is made of a polyolefin material.
57. The sample vial of paragraph 56, wherein the polyolefin material is a polypropylene material.
58. The sample vial of any one of paragraphs 1-57, wherein the sample vial is made of a material of construction selected from the group consisting of styrene acrylonitrile (SAN) polymers, polycarbonates, copolyesters (e.g., Eastman Tritan™ copolyester), and other hydrophilic polymers that retain adequate optical transparency for observation of contents in the cavity.
59. The sample vial of any one of paragraphs 1-58, having a burst pressure of at least 0.1 MPa and preferably at least 0.2 MPa from pressurization of the cavity, and optionally not larger than 1 MPa.
60. The sample vial of any one of paragraphs 1-59, wherein a volume of fluid sample is disposed in the cavity of the sample vial, and optionally the volume of the fluid sample is in a range having a lower limit of 150 microliters, 250 microliters, or 300 microliters and an upper limit of 600, microliters, 500 microliters or 400 microliters.
61. The sample vial of paragraph 60, wherein the fluid sample comprises unassociated particles of biological material for analysis, the unassociated particles optionally having a size with a maximum cross dimension in a range of from 20 nanometers to 1 micrometer.
62. The sample vial of paragraph 61, wherein the unassociated particles are selected from the group consisting of virions, virus-like particles and extracellular vesicles.
63. The sample vial of either one of paragraph 61 or paragraph 62, wherein the unassociated particles are labeled with a fluorescent stain.
64. An analytical sample delivery vessel comprising a sample vial of any one of paragraphs 1-63 and a cap covering the open end of the cavity.
65. The analytical sample delivery vessel of paragraph 64, comprising a septum in the cap for insertion of an analytical instrument sample feed probe through the cap and into the cavity.
66. An array of sample vials for automated processing of a plurality fluid samples for analysis by an analytical instrument, the array comprising:
67. The array of paragraph 66, wherein each said sample vial received in the received position is in a sample delivery vessel of either one of paragraph 64 or paragraph 65.
68. The array of either one of paragraph 66 or paragraph 67, wherein each said receptacle comprises a rotational stop feature engaged with a corresponding said sample vial in the received position, the rotational stop feature comprising at least one engagement protrusion that is disposed in a said exterior recess between a pair of said ribs of the said sample vial in the received position, wherein the said sample vial in the received position is prevented from fully rotating relative to the corresponding said receptacle.
69. A kit for handling a plurality of fluid samples for analytical evaluation, the kit comprising:
70. The kit of paragraph 69, comprising a plurality of caps corresponding to the plurality of the sample vials, each said cap adapted to engage with a said sample vial to cover the cavity from above in the working orientation.
71. The kit of paragraph 70, wherein the caps are engaged with a corresponding plurality of the sample vials.
72. The kit of any one of paragraphs 69-71, comprising the plurality of said sample vials received in a corresponding plurality of said receptacles in the received position, with a said rotational stop feature engaged with a said sample vial to prevent full rotation of the said sample vial relative to the receptacle.
73. The kit of any one of paragraphs 69-72, wherein the plurality of sample vials and the tray are in the form of the array of any one of paragraphs 66-68.
74. The array or kit of any one of paragraphs 68-73, wherein a said sample vial received in the received position in a corresponding said receptacle is prevented by the rotational stop feature from rotating relative to the corresponding said receptacle by more than 180°, preferably by more than 90°, more preferably by more than 45°, even more preferably by more than 15° and still more preferably by more than 5°, about the longitudinal axis.
75. The array or kit of any one of paragraphs 68-74, wherein the rotational stop feature comprises a plurality of said engagement protrusions with each said engagement protrusion disposed between a different pair of said ribs.
76. The array or kit of any one of paragraphs 66-75, wherein in the received position at least a distal portion of the ribbed exterior of a said sample vial is disposed in a corresponding said receptacle.
77. The array or kit of any one of paragraphs 66-76, wherein:
78. The array or kit of any one of paragraphs 66-77, wherein;
79. The array or kit of paragraph 78, wherein the cylindrical envelope radius of the sample vial is from the longitudinal axis to a maximum projection of a rib radially from the longitudinal axis.
80. The array or kit of any one of paragraphs 77-79, wherein in the received position the longitudinal axis of a said sample vial is coaxial with a central longitudinal axis of a said corresponding receptacle.
81. An analytical system for analysis of one or more properties of a fluid sample, the analytical system comprising;
82. A method for analyzing a fluid sample, the method comprising:
83. The method of paragraph 82, comprising investigating material of the fluid sample in the investigation zone and collecting data from the investigation zone on at least one property of investigated material.
84. The method of either one of paragraph 82 or paragraph 83, wherein the analysis volume is in a range having a lower limit of 50 microliters or 100 microliters and an upper limit of 595 microliters or 400 microliters.
85. The analytical system or method of any one of paragraphs 81-84, wherein:
86. The analytical system or method of paragraph 85, comprising a fluid seal between the engagement structure of the sample vial and the corresponding engagement structure of the analytical instrument.
87. The analytical system or method of either one of paragraph 85 or paragraph 86, wherein the engagement structure of the sample vial and the corresponding engagement structure of the analytical instrument comprise corresponding threaded structures that are rotatably engaged to fluidly connect the fluid cavity with the fluid path of the analytical instrument.
88. The analytical system or method of any one of paragraphs 81-87, wherein the sample vial is in the array of any one of paragraphs 66-68 and 74-80.
89. The analytical system or method of any one of paragraphs 81-88, wherein the analytical instrument comprises a flow cytometer comprising the investigation zone.
90. An analytical system of any one of paragraphs 81-88, wherein the analytical instrument comprises a chromatograph comprising the investigation zone.
91. A method of handling a plurality of fluid samples for analytical evaluation, comprising:
92. The method of paragraph 91, wherein the capping comprises engaging the cap with the said sample vial and rotating the engaged cap relative to the said sample vial while the said sample vial is prevented from rotating in the receptacle by the rotational stop feature.
93. The method of paragraph 92, wherein the rotating is performed by an automated processing system.
94. The method of any one of paragraphs 91-93, comprising completing disposing a said volume of fluid sample in each of the plurality of the sample vials before performing the capping of any said sample vial, wherein all of the plurality of sample vials are filled with a said volume of fluid sample prior to commencement of the capping.
95. A method for making the sample vial of any one of paragraphs 1-59, comprising molding the sample vial as a single-piece molded structure from a plastic material. 96. The method of paragraph 95, wherein the plastic material is a thermoplastic material.
97. The method of either one of paragraph 95 or paragraph 96, wherein the molding comprises injection molding.
The terms “comprising”, “containing”, “including” and “having”, and grammatical variations of those terms, are intended to be inclusive and nonlimiting in that the use of such terms indicates the presence of a stated condition or feature, but not to the exclusion of the presence also of any other condition or feature. The use of the terms “comprising”, “containing”, “including” and “having”, and grammatical variations of those terms in referring to the presence of one or more components, subcomponents or materials, also include and is intended to disclose the more specific embodiments in which the term “comprising”, “containing”, “including” or “having” (or the variation of such term) as the case may be, is replaced by any of the narrower terms “consisting essentially of” or “consisting of” or “consisting of only” (or any appropriate grammatical variation of such narrower terms). For example, a statement that something “comprises” a stated element or elements is also intended to include and disclose the more specific narrower embodiments of the thing “consisting essentially of” the stated element or elements, and the thing “consisting of” the stated element or elements. Examples of various features have been provided for purposes of illustration, and the terms “example”, “for example” and the like indicate illustrative examples that are not limiting and are not to be construed or interpreted as limiting a feature or features to any particular example. The term “at least” followed by a number (e.g., “at least one”) means that number or more than that number. The term at “at least a portion” means all or a portion that is less than all. The term “at least a part” means all or a part that is less than all. The term “at least a majority” means all or a majority part that is less than all.