CN116648612A

CN116648612A - Sample transport medium tube

Info

Publication number: CN116648612A
Application number: CN202180082661.1A
Authority: CN
Inventors: 凌明夫
Original assignee: Individual
Current assignee: Individual
Priority date: 2020-10-09
Filing date: 2021-10-08
Publication date: 2023-08-25

Abstract

A sample collection kit comprising a sample transport medium tube, a transport medium, and a swab for collecting a sample. The transport medium compartment of the sample transport medium tube has a reduced inner diameter and contains a reduced volume of the transport medium compared to conventional transport medium tubes. The tip of the swab containing the collected sample stored in the sample transport medium tube may remain submerged in the transport medium during transport to the test facility, preventing drying of the swab tip and degradation of the sample. In addition, the relatively small volume of transport medium in the tube reduces dilution of analytes from the sample in the transport medium.

Description

Sample transport medium tube

Background

The present application relates to a device for storing and transporting collected samples. More particularly, the present application relates to improved transport media (transport media) tubes for storing and transporting samples collected on swabs, and to sample collection kits containing such tubes.

A sample or specimen is often required to predict or diagnose a disease or condition in a subject in need of care. The sample may be collected in a medical facility (e.g., a hospital or clinic) or in any number of environments, such as the subject's home, workplace, or community. Samples, such as from the buccal surface, nasopharynx, wound, blood stain, or drop, may be collected from the tip of the swab with an absorbent material (e.g., nylon). Nasopharyngeal swabs have been used to collect samples from the nasopharynx to test for the presence of covd-19 and influenza virus, etc. Oropharyngeal swabs have also been used to collect samples from the oropharynx for testing of covd-19 and influenza viruses, among others. The collected swab (in particular, the swab tip) is then immersed in a transport medium in a closed container in the form of a tube to preserve the collected sample. The collected swab immersed in the transport medium tube is then transported to a laboratory where laboratory tests will be performed. The sample collected on the swab tip in the tube is eluted into the transport medium. Once received in the laboratory, the shipping medium is subjected to various laboratory tests. Depending on the particular purpose of the laboratory test, the presence or concentration of analytes, RNA, DNA, proteins, lipids, carbohydrates and other molecules, or the quantification or identification of live viruses, bacteria, fungi and other microorganisms, may be determined.

Currently, in order to collect a sufficient amount of sample from a subject, the swab tip need not only be made of an absorbent material, but also have sufficient surface area to collect the sample (e.g., the length of the swab tip is typically between 10 and 25mm, and the diameter of the swab tip is typically between 3 and 6 mm). Because the swab tip needs to be completely submerged in the transport medium in the tube to hold the sample, 1ml, 2ml or 3ml of transport medium is currently required in sample collection systems. The required volume of transport medium is determined by the diameter of the transport medium tube. Table 1 provides examples of shipping media volumes for commercial universal shipping media (UTM) products.

Table 1: investigation of transport Medium volumes in commercial Universal transport Medium products

In addition, the known transport media tubes need to be long in order to cover the length of the swab within the transport media tube. For example, kepanen Corp302C virus transport medium 1ml or 3ml of transport medium is provided in a 16mm diameter by 100mm length tube, providing an internal chamber space volume of about 20ml, including the air space plus transport medium volume. In such transport medium tubes, there is a large in-tube air space above the transport medium (17 ml for 3ml transport medium or 19ml for 1ml transport medium). However, during transport of the transport medium tube (especially by mail or express service), it is likely that the tube will be sideways or even inverted, with the effect that the collected sample swab tip may not be immersed in the transport medium for several hours or even more. If the swab tip is not immersed in the transport medium during transport or storage, dehydration of the collected sample swab tip and degradation of the pathogen sample may occur, leading to false negative results.

In contrast, current molecular diagnostic tests or assays, including nucleic acid detection, require or use only a small portion of the volume of the transport medium collected. For example, most molecular diagnostic tests (DNA detection analysis and RNA detection analysis by PCR or RT-PCR) use only up to 200 μl or even less (20-100 μl) of the collected transport medium (see table 2). Furthermore, the nucleic acid isolated from this 20-200. Mu.l of the collected transport medium may even carry 3 or more repeated sequences for nucleic acid detection analysis.

Table 2: investigation of sample input volumes in DNA/RNA separation methods

Not only molecular diagnostic tests (PCR-based methods), but virologic or microbiological studies also require small volumes of collected transport medium for laboratory testing. For example, for chlamydia trachomatis (Chlamydia trachomatis) and neisseria gonorrhoeae (Neisseria gonorrhoeae) detection, only up to 200 μl is required for plating or inoculation. In view of the above, more than 200. Mu.l of the collected transport medium is generally not required for laboratory testing. Thus, one major problem with collecting swabs in a volume of 1-3ml of shipping medium instead of 100-200 μl of the required test volume is that the sample collected on the swab is unnecessarily diluted in the shipping medium, resulting in a low titer of pathogen sample, which can result in a concentration or amount below the detection limit of the current assay, leading to further false negative results.

Obviously, this problem cannot be solved by simply reducing the volume of the transport medium placed in a conventional prior art transport medium tube characterized by a diameter of more than 10mm, and typically 16 mm. As shown in table 3 below, a minimum of 2ml of shipping medium is required in conventional prior art shipping medium tubes to reach a medium fill height of 11.3mm in order to cover a 10mm length swab tip.

Table 3: culture medium filling height of various culture medium volumes in 15mm inner diameter tube of the prior art

Volume (mL)	0.4	0.6	0.8	1	2
						Height of filling with culture Medium (mm)	2.3	3.4	4.5	5.7	11.3

Because the length of the swab tip is typically between 10-25mm, if the prior art sample collection tube is used with a small volume of shipping medium (e.g., less than 2 ml), the height of the shipping medium will not be sufficient to cover most or all of the length of the swab tip, even when the tube remains upright. If the tube should be sideways, the media coverage of the swab tip will be even lower. Thus, the swab and the sample collected on the swab will be at risk of dehydration and degradation.

Accordingly, there is a need to address the above problems and to improve the design of sample collection kits and methods or processes of sample collection to aid in diagnosing diseases or conditions in a subject in need thereof.

Disclosure of Invention

In one aspect, the present invention provides a specimen transport media tube for transporting a specimen disposed on a swab tip of a swab. The sample transport media tube includes a mouth end having an opening configured to receive a swab tip, a distal end opposite the mouth end to define a longitudinal axis of the sample transport media tube, and at least one sidewall extending longitudinally between the mouth end and the distal end to define and enclose an interior space within the sample transport media tube. The interior space is in fluid communication with the opening of the mouth end. The tube also includes a cap configured to engage the mouth end to seal the opening.

The interior space of the sample transport medium tube includes a mouth at a mouth end, a transport medium compartment longitudinally aligned with the longitudinal axis of the tube, and a tapered portion disposed between the mouth and the transport medium compartment in fluid communication with both the mouth and the transport medium compartment. The swab tip may pass through the opening into the mouth and through the tapered portion without obstruction to be received in the transport medium compartment. The transport medium compartment may also contain transport medium. The cap includes a cap insert configured to prevent fluid communication between the mouth and the transport medium compartment when the cap is engaged with the mouth.

The transport medium compartment has an inner diameter smaller than the inner diameter of the mouth. The inner diameter of the tapered portion decreases from the inner diameter of the mouth at the junction between the tapered portion and the mouth to the inner diameter of the transport medium compartment at the junction between the tapered portion and the transport medium compartment. In at least one embodiment, the inner diameter of the transport medium compartment is less than or equal to 10mm. In at least one embodiment, the interior volume of the transport medium compartment is less than 1ml.

Another aspect of the invention provides a sample collection kit comprising a sample transport medium tube, transport medium, and swab as described herein. In at least one embodiment, the kit further comprises instructions for use of the kit. In at least one embodiment, the transport medium is contained within a transport medium compartment of a sample transport medium tube. In at least one embodiment, the swab is attached to the cap of the sample transport medium tube. In at least one embodiment, the swab is a nasopharyngeal swab. In at least one embodiment, the swab is an oropharyngeal swab.

Drawings

Other features of the present invention will become apparent from the following written description and the accompanying drawings, in which:

FIG. 1A is a side view of an embodiment of a sample collection kit according to the present application.

FIG. 1B is a side view of an alternative embodiment of a sample collection kit according to the present application.

FIG. 1C is a side view of an alternative embodiment of a sample collection kit according to the present application.

Fig. 2A is a side view of an alternative embodiment of a sample collection kit according to the present application.

FIG. 2B is a side view of an alternative embodiment of a sample collection kit according to the present application.

Fig. 2C is a side view of an alternative embodiment of a sample collection kit according to the present application.

Fig. 2D is a side view of an alternative embodiment of a sample collection kit according to the present application.

Fig. 3A is a side view of the embodiment of fig. 1A in use.

Fig. 3B is an alternative side view of the embodiment of fig. 1A in use.

Fig. 3C is an alternative side view of the embodiment of fig. 1A in use.

Fig. 4A is an alternative side view of the embodiment of fig. 1A in use.

Fig. 4B is an alternative side view of the embodiment of fig. 1A in use.

Fig. 4C is an alternative side view of the embodiment of fig. 1A in use.

Fig. 5A is a side view of the embodiment of fig. 2A in use.

Fig. 5B is an alternative side view of the embodiment of fig. 2A in use.

Fig. 5C is an alternative side view of the embodiment of fig. 2A in use.

Fig. 5D is an alternative side view of the embodiment of fig. 2A in use.

Fig. 6A is a side view of an alternative embodiment of a sample collection kit according to the present application.

Fig. 6B is a side view of the embodiment of fig. 6A in use.

Fig. 6C is an alternative side view of the embodiment of fig. 6A in use.

Fig. 6D is an alternative side view of the embodiment of fig. 6A in use.

Fig. 6E is an alternative side view of the embodiment of fig. 6A in use.

Fig. 6F is an alternative side view of the embodiment of fig. 6A in use.

Fig. 7A includes side, perspective, top, bottom and cross-sectional views of the cap insert head of the embodiment of fig. 6A.

Fig. 7B is a top view of the cap insert head of the embodiment of fig. 6A enclosing a swab handle in an uncompressed state.

Fig. 7C is a top view of the cap insert head of the embodiment of fig. 6A enclosing the swab handle in a compressed state.

Fig. 8A is a side view of an alternative embodiment of a sample collection kit according to the present application.

Fig. 8B is a side view of the embodiment of fig. 8A in use.

Fig. 8C is an alternative side view of the embodiment of fig. 8A in use.

Fig. 8D is an alternative side view of the embodiment of fig. 8A in use.

Fig. 8E is an alternative side view of the embodiment of fig. 8A in use.

Fig. 9A includes side, perspective, top, bottom and cross-sectional views of the cap insert head of the embodiment of fig. 8A.

Fig. 9B is a top view of the cap insert head of the embodiment of fig. 8A enclosing a swab handle in an uncompressed state.

Fig. 9C is a top view of the cap insert head of the embodiment of fig. 8A enclosing the swab handle in a compressed state.

Detailed Description

In at least one embodiment, the present invention provides a sample collection kit for collecting, storing, preserving, and/or transporting a collected sample or specimen. The sample may be any specimen that may be collected on a swab. For example, a sample may be collected by contacting the surface with a swab to transfer material from the surface to the swab tip or exposing the swab to a fluid such that a portion of the fluid is absorbed on the swab tip. Surfaces that may be sampled include, but are not limited to, surfaces in an environmental or industrial setting (e.g., home, workplace, or community), or surfaces found on or in biological organisms, including, but not limited to, mucosal surfaces such as oral, buccal, nasal, pharyngeal, aural, urethral, anal and vaginal surfaces, skin, and other surfaces. Fluids that may be sampled include, but are not limited to, fluids found in environmental or industrial settings (e.g., home, workplace, or community), fluids exposed to or containing biological materials (including, but not limited to, microorganisms), and fluids derived from biological organisms or microorganisms, including, but not limited to, secretions from mucosal surfaces or tracts or from wounds, blood, urine, and other biological fluids or secretions.

In at least one embodiment, samples may be obtained for laboratory testing, including but not limited to analysis, microbiology, molecular diagnostics, and other examinations. Such tests include, but are not limited to, testing for the presence or concentration or amount of an analyte. As used herein, the term "analyte" means any material or substance whose presence, amount, or concentration is subject to measurement, and includes, but is not limited to, cells; microorganisms, including but not limited to viruses, bacteria, fungi, and other microorganisms; and molecular analytes including, but not limited to, RNA, DNA, proteins, lipids, carbohydrates, and other chemicals.

The sample collection kit includes a sample transport medium tube, transport medium, and a swab for collecting a sample or specimen. The swab has an elongated swab handle attached at least one end to the swab tip and may be a conventional swab well known in the art. In at least embodiments, the swab handle is cylindrical or prismatic. In at least one embodiment, the length of the swab, including the handle and swab tip, is in the range of about 7.5cm to about 15cm as desired to allow the user to conveniently place the swab tip in a position to collect a desired sample in a site with limited accessibility, including but not limited to the inner lumen of the nose, mouth, pharynx, ear, rectum, urethra, vagina, or other lumen. In at least one embodiment, the swab handle is made of plastic, wood, paper, glass, or metal. In at least one embodiment, the swab handle is made of an elastic material, including but not limited to a plastic material such as polypropylene, polystyrene, or Acrylonitrile Butadiene Styrene (ABS) plastic.

In at least one embodiment, the swab handle has a narrowed region or breaking point that helps to break the handle so that the shortened swab, including the swab tip and the shortened portion of the handle attached to the swab tip, can be separated from the rest of the handle distal to the swab tip. In at least one embodiment, the breaking point is located about 1cm to about 9cm from the swab end at the swab tip, such that the net length of the shortened swab may be in the range of about 1cm to about 9cm after the handle breaks at the breaking point. In at least one embodiment, the breaking point is located about 3cm to about 9cm from the swab end at the swab tip, such that the net length of the shortened swab may be in the range of about 3cm to about 9cm after the handle breaks at the breaking point. As used herein, the term "clear length of the swab" means the total length of the swab tip and the attached handle, or the total length of the attached portion of the swab tip and the broken handle after the handle breaks at the breaking point. In at least one embodiment, the breaking point may be located about 3cm from the swab end at the swab tip, such that the net length of the swab is about 3cm. In at least one embodiment, the breaking point may be located about 7.5cm to about 9cm from the swab end at the swab tip, such that the net length of the swab is about 7.5cm to about 9cm.

In at least one embodiment, the swab tip is made of a material suitable for absorbing or incorporating a desired sample, as will be appreciated in the art. In at least one embodiment, the material is porous or fibrous. In at least one embodiment, the material is hydrophilic so as to readily absorb or incorporate aqueous or other hydrophilic samples during collection. In at least one embodiment, the material is hydrophobic, so any collected hydrophilic sample is more easily released from the swab tip and dissolves into the hydrophilic transport medium in which the swab tip is submerged. Those skilled in the art will be readily able to select a swab with the appropriate material at the swab tip for a particular application. Suitable materials for the swab tip include, but are not limited to, cotton-like materials, rayon, wool, nylon, porous plastic sponge materials (including, but not limited to, polyethylene), and other materials well known in the art. The swab tip is attached to the handle by any means known in the art. For example, the material comprising the swab tip may be wrapped around the handle or attached to the handle by flocking or with an adhesive.

In at least one embodiment, the specimen transport media tube includes a mouth end, a distal end opposite the mouth end and defining a longitudinal axis therewith, and at least one sidewall extending longitudinally between the mouth end and the distal end to form a tubular structure, thereby defining and enclosing an interior space within the specimen transport media tube. Each of the at least one side wall of the sample transport medium tube may be planar or arcuate such that the sample transport medium tube has a circular or polygonal cross section at any point along its length, so long as the interior space of the sample transport medium tube is enclosed by the mouth end, the distal end and the at least one side wall. In at least one embodiment, the mouth end includes an opening configured to receive a swab containing a collected sample. In at least one embodiment, the interior space includes a mouth at the mouth end of the tube in fluid communication with the opening at the mouth end so as to allow free flow of gas, liquid or other fluid therebetween.

In at least one embodiment, the interior space further includes a transport medium compartment configured to hold a transport medium, as will be described more fully below, and having an inner diameter that is less than an inner diameter of the mouth. The transport medium compartment of the interior space is longitudinally aligned within the longitudinal axis of the specimen transport medium tube and has a first end in fluid communication with the mouth end of the tube and a second end defined by the distal end of the tube. At least one tapered or stepped sidewall extends between the at least one sidewall of the mouth and the at least one sidewall of the transport medium compartment to form a tapered or stepped portion of the interior space of the tube having a tapered transverse diameter or width between the mouth and the first end of the transport medium compartment. In at least one embodiment, the inner diameter of the mouth end of the sample transport medium tube is from about 18mm to about 21mm. In at least one embodiment, the transport medium compartment has an inner diameter of less than about 10mm. In at least one embodiment, the mouth of the sample transport medium tube and transport medium compartment can be cylindrical or prismatic, while the tapered or stepped portion can be conical or polyhedral.

In at least one embodiment, the distal end of the sample transport medium tube includes a distal wall that is perpendicular to the longitudinal axis of the sample transport medium tube and integral with at least one sidewall at the distal end of the sample transport medium tube such that the distal end of the tube is closed and fluid communication between the exterior of the tube and the interior space of the tube (including the transport medium compartment) is prevented. In at least one embodiment, the distal end of the sample transport medium tube has an opening that allows fluid communication between the exterior of the tube and the interior space of the tube (including the transport medium compartment). In such embodiments, the sample transport medium tube may further include a removable and replaceable distal cap that engages one or more sidewalls at the distal end of the tube, thereby functioning to seal the opening at the distal end of the tube, e.g., preventing transport medium from being lost from the transport medium compartment during transport of the tube. For example, removal of the distal cap may facilitate retrieval of the shipping medium from the shipping medium compartment for analysis. In some embodiments, the distal cap may engage one or more sidewalls at the distal end of the tube by means of helical threads configured to mate with complementary helical threads on one or more sidewalls at the opening at the distal end of the sample transport medium tube. In at least one alternative embodiment, the distal cap may snap tightly over one or more sidewalls at the opening, be inserted tightly within the opening, or engage one or more sidewalls at the distal end of the tube and seal the opening by other methods well known in the art. Suitable materials for the distal cap include, but are not limited to, rubber, silicone, and moldable plastic materials, including, but not limited to, polystyrene, polypropylene, and other moldable plastic materials, as are well known in the art.

It will be apparent to the skilled artisan that in view of the reduced inner diameter of the transport medium compartment as compared to the inner diameter of the mouth of the sample transport medium tube, in at least one embodiment, the distal end of the sample transport medium tube may have a width or diameter that is less than the width or diameter of the mouth end of the tube. In at least one such embodiment, the specimen transport media tube can include a support structure at its distal end to provide greater stability to the specimen transport media tube when the specimen transport media tube is resting upright on its distal end. In at least one embodiment, the support structure comprises a planar base having a width or diameter greater than a width or diameter of the distal end of the specimen transport medium tube and oriented perpendicular to the longitudinal axis of the specimen transport medium tube. In at least one embodiment, the support structure may be integral with at least one sidewall at the distal end of the specimen transport medium tube. In at least one embodiment, the support structure may be integral with the distal cap or secured to the distal cap. Suitable materials for the support structure include, but are not limited to, glass and moldable plastic materials, including, but not limited to, polypropylene and other moldable plastic materials, as is well known in the art.

In at least one alternative embodiment, the sample transport medium tube may include one or more additional outer side walls that extend parallel to the longitudinal axis from the mouth end of the tube to the distal end of the tube. In at least one embodiment, at least one of the exterior sidewalls may provide a surface on which sample authentication details may be recorded, for example, by writing or attaching a label, or on which a barcode label may be attached. In at least one embodiment, at least one of the outer sidewalls can facilitate handling of the sample transport medium tube by an automated robotic liquid handling system. For example, in at least one embodiment, at least one outer sidewall may provide a surface that facilitates gripping of a sample transport medium tube by a robotic arm.

In at least one embodiment, one or more outer side walls terminate at or beyond the distal end of the tube to form an opening such that the distal end of the tube and the distal cap (if present) are accessible outside the tube. In at least one embodiment, the opening formed by the outer side walls at the distal end of the tube has a width or diameter substantially equal to and parallel to the cross-sectional width or diameter of the tube at the mouth end, and thus, the ends of the outer side walls define a planar surface perpendicular to the longitudinal axis of the specimen transport medium tube and can act as a support structure for the specimen transport medium tube, allowing the tube to stand upright at its distal end. In at least one embodiment, the ends of the one or more outer side walls may be enclosed by an outer distal wall extending perpendicular to the longitudinal axis of the specimen transport medium tube to form a flat support surface enclosing the distal end of the specimen transport medium tube, again allowing the tube to stand upright at its distal end. In at least one embodiment, the flat support surface formed by the outer distal wall at the distal end of the tube has a width or diameter substantially equal to the width or diameter of the tube at the mouth end and may act as a support structure for the sample transport medium tube.

In at least one embodiment, the specimen transport medium tube includes a removable and replaceable cap configured to engage one or more sidewalls at the mouth end of the tube, thereby sealing the opening at the mouth end of the tube. In at least one embodiment, the cap includes helical threads configured to mate with complementary helical threads on one or more sidewalls at the opening at the mouth end of the sample transport medium tube, thereby sealing the opening, as is well known in the art. In at least one alternative embodiment, the cap may snap tightly over one or more sidewalls at the opening, be tightly inserted within the opening, or otherwise seal the opening, as will be well understood by the skilled artisan. Suitable materials for the cap include, but are not limited to, moldable plastic materials, as are well known in the art, including, but not limited to, polypropylene and polyethylene terephthalate.

In at least one embodiment, the cap includes a cap insert that inserts into the mouth of the tube when the cap is engaged with one or more sidewalls at the mouth end of the specimen transport medium tube. The cap insert may be fixed to or integral with the cap or may engage the cap when the cap is secured over the opening at the mouth end of the sample transport medium tube. If the cap insert is fixed to or integral with the cap, it should be configured so as not to interfere with engagement of the cap with the one or more sidewalls at the mouth end of the tube. In at least one embodiment, the cap insert is inert to the shipping medium such that it does not significantly degrade and does not cause significant degradation of the shipping medium upon contact with the shipping medium. Suitable materials for the cap insert include, but are not limited to, silicone, rubber, or plastic, including, but not limited to, polypropylene and polyethylene. The cap insert may be manufactured using plastic injection molding techniques, as is well known in the art.

The cap insert may comprise a cap insert head which, when the cap is secured over the opening to the mouth of the sample transport medium tube, sits snugly within the tapered or stepped portion of the tube, or against or into the tapered or stepped portion of the sample transport medium tube within the opening of the transport medium compartment, so as to seal the interface between the transport medium compartment and the tapered or stepped portion of the sample transport medium tube and prevent transport medium contained in the transport medium compartment from escaping or leaking from the transport medium compartment of the tube. In at least one embodiment, the cap insert head has a profile that is complementary to the internal profile of the tapered or stepped portion of the specimen transport tube so as to fit snugly thereon.

In at least one embodiment, the cap insert head is made of a material inert to the transport medium such that it does not significantly degrade and does not cause significant degradation of the transport medium upon contact with the transport medium, and it is resiliently compressible to conform to the shape of the tapered or stepped portion of the tube or to fit tightly within the opening of the transport medium compartment and to fill any gaps or air spaces that might otherwise allow the transport medium to flow, thereby sealing the interface between the transport medium compartment and the tapered or stepped portion of the sample transport medium tube. As used herein, the term "elastically compressible" means that a material is flexible and can decrease in volume when subjected to pressure, but is elastic in its compressed state so as to fully occupy its available reduced volume.

The cap insert head may take a variety of shapes as long as the cap insert head is used to seal the interface between the transport medium compartment and the tapered or stepped portion of the sample transport medium tube and prevent the transport medium contained in the transport medium compartment from escaping from the transport medium compartment and entering the mouth of the tube. In at least one embodiment, the cap insert head includes an O-ring or circular or tape-shaped gasket (gasset) mounted on the cap insert such that the O-ring or circular or tape-shaped gasket fits tightly within the tapered or stepped portion of the interior space of the tube or within the opening at the first end of the transport medium compartment. In at least one embodiment, the O-ring is positioned about 1mm to about 7mm above the distal end of the cap insert such that it closely contacts the inner sidewall of the tapered or stepped portion of the specimen transport medium tube.

The cap insert head may be manufactured using plastic injection molding techniques, as is well known in the art. When the cap insert head includes an O-ring, the O-ring may be manufactured by extrusion, injection molding, pressure molding, or transfer molding, as is known in the art. Suitable materials for the cap insert head include, but are not limited to, silicone, rubber, vulcanized material, or plastic, including, but not limited to, polypropylene. The cap insert and cap insert head may vary in shape and may be solid or hollow in their interior, so long as the cap insert head can be positioned to seal the opening of the transport medium compartment and prevent transport medium from being lost therefrom.

In use, the larger diameter of the mouth and the presence of the tapered portion allows the user to more easily insert the swab tip containing the collected sample into the sample transport medium tube and guide the swab tip into place in the transport medium compartment. Once the swab tip is placed in the transport medium compartment containing the transport medium, the handle may be conveniently broken at the point of break or cut at any convenient point on the handle to form a shortened swab, such that the swab tip in the transport medium compartment is attached to only a short portion of the handle that remains with the swab tip after breaking. The cap may then be secured over the mouth of the specimen transport medium tube such that the cap seals the opening at the mouth end of the tube and the cap insert head seals the interface between the transport medium compartment and the tapered or stepped portion of the specimen transport medium tube. In at least one embodiment, the cap is secured to the mouth of the specimen transport medium tube by engaging a helical thread on the cap with a complementary helical thread on one or more side walls of the mouth.

Thus, in at least one embodiment, the sample transport medium tube has a length sufficient to include the net length of the swab. In at least one embodiment, the length of the sample transport medium tube will exceed the clear length of the swab by at least 5mm. In this way, the clear length of the swab may be fully contained within the sample transport medium tube. In at least one embodiment, the length of the specimen transport medium tube is from about 90mm to about 95mm.

It is contemplated that the portion of the swab handle that remains with the swab tip in the swab or shortened swab may be entirely contained within the transport medium compartment, or that the portion of the swab handle may extend into the mouth of the tube. In some embodiments where the swab handle extends into the mouth of the tube, when in place, the cap insert head may move the handle toward the inside wall of the tapered or stepped portion of the tube, and the cap insert head may deform around the handle so as to seal the opening of the transport medium compartment. In embodiments where the cap insert head is an O-ring, the O-ring preferably has a cross-sectional diameter of at least 1.5mm or at least 2mm to have sufficient resilient compressibility to deform around the handle and seal the opening of the transport medium compartment.

In some embodiments, the cap insert head may have a groove or slit to tightly enclose the swab handle, allowing for sealing of the opening of the transport medium compartment. The cap insert may further include a retaining clip or clip to retain the swab handle, as discussed in further detail below. Such embodiments are suitable for accommodating swabs, such as nasopharyngeal swabs, having a resilient handle or a handle with a smaller diameter along at least a portion of the length of the handle adjacent the swab tip.

In at least one alternative embodiment in which the swab handle extends into the mouth of the tube, the cap insert may include a central longitudinal channel through which the swab handle may pass, and which forms a seal around the swab handle to prevent transport medium from passing from the transport medium compartment through the central longitudinal channel into the mouth of the sample transport medium tube. Such embodiments are suitable for receiving swabs, such as oropharyngeal swabs, having a less resilient handle or having a handle with a larger diameter.

As used herein, the term "transport medium" means a fluid in which the swab tip is placed after a sample or specimen has been collected using the swab. In at least one embodiment, the shipping medium provides an environment in which any microorganisms or cells present on the swab tip can remain viable for further culture or growth. In at least one embodiment, the shipping medium provides an environment in which any microorganisms or cells present on the swab tip may be stored in a live, dead or dormant state for further examination or analysis. In at least one embodiment, the transport medium provides an environment that prevents the analytes present on the swab tip from undergoing degradation or decomposition.

In at least one embodiment, the transport medium is aqueous. In at least one embodiment, the shipping medium may contain additives including, but not limited to, nutrients, buffers, salts, antimicrobial agents, preservatives, agents and other additives well known in the art. Suitable preservatives for preserving biodegradable analytes such as proteins, DNA and RNA include, but are not limited to, denaturants including, but not limited to, sodium Dodecyl Sulfate (SDS) and chaotropes including, but not limited to, guanidine hydrochloride, guanidine thiocyanate, and alcohols. Suitable shipping media are well known and/or commercially available in the art and include, but are not limited to, saline, phosphate buffered saline, universal shipping media, viral shipping media, guanidine-containing media, propagation shipping media, non-propagation shipping media, anaerobic shipping media, charcoal shipping media, bacterial shipping media, and other shipping media well known in the art.

The transport medium compartment of the sample transport medium tube of the present invention has a reduced inner diameter compared to the inner diameter of conventional transport medium tubes. In this way, the volume of transport medium contained within the transport medium compartment is relatively small so as not to over-dilute the sample collected on the swab tip, but is sufficient to submerge the entire length of the swab tip in order to maintain the collected sample exposed to the transport medium regardless of the direction or position of gravity of the sample transport medium tube during transport. Table 4 provides examples of the volumes of shipping medium required in the shipping medium compartments having various inner diameters in order to achieve a media fill height sufficient to submerge various lengths of swab tips.

Table 4: volumes of transport medium required to achieve 10, 15, 20 and 25mm medium fill height with various tube inner diameters

Thus, for example, for a transport medium compartment with a 9mm inner diameter, only 0.64ml of transport medium is required in order to have a medium filling height of 10 mm. Alternatively, up to 1.59ml of shipping medium is required to provide a medium fill height of 25 mm. In another example, for a shipping medium compartment with a 7mm inside diameter, 0.38ml of shipping medium is required to have a medium fill height of 10mm, and 0.96ml of shipping medium is required to provide a medium fill height of 25 mm.

Notably, when the swab is inserted into the shipping medium, it displaces a volume of the shipping medium. For example, in an experiment, a nasopharyngeal swab having a swab tip length of 23mm and a diameter of 3mm was inserted into a container having 0.4ml of water having an inner diameter of 6mm and a length of 100mm, and was found to displace 0.06ml of water. A swab tip considered to carry a biological sample having a higher viscosity than water may have an even higher displacement volume. The displacement volume of transport medium for other sizes of sample transport medium tubes can be readily determined experimentally by those skilled in the art without undue effort or creative skill requirements. Thus, considering this displaced volume, the target medium fill height can be achieved using even lower volumes of shipping medium than those listed in table 4 above.

Thus, in at least one embodiment, the transport medium compartment has an inner diameter of less than or equal to 10 mm. In at least one embodiment, the transport medium compartment has an inner diameter of less than or equal to 8 mm. In at least one embodiment, the transport medium compartment has an inner diameter of less than or equal to 6 mm. In at least one embodiment, the transport medium compartment has an inner diameter of less than or equal to 5 mm. In at least one embodiment, the transport medium compartment has an inner diameter of less than or equal to 4 mm. Additionally, in at least one embodiment, the transport medium compartment has a length sufficient to accommodate the entire length of the swab tip. Thus, in at least one embodiment, the transport medium compartment has a length of about 10mm to about 40 mm. In one embodiment, the transport medium compartment has a length of about 30 mm. In one embodiment, the transport medium compartment has a length of about 35 mm. In at least one embodiment, the transport medium compartment has a volume sufficient to hold a volume of transport medium less than or equal to 1 ml. In at least one embodiment, at least 66% of the length of the swab tip is submerged in the shipping medium when the swab tip is fully inserted into the shipping medium compartment filled with shipping medium. In at least one embodiment, at least 90% of the length of the swab tip is submerged in the shipping medium when the swab tip is fully inserted into the shipping medium compartment filled with shipping medium.

In at least one embodiment, the transport medium compartment contains a volume of transport medium that is less than the available volume inside the compartment, such that the compartment also contains a volume of air. In such embodiments, when the swab is inserted into the transport medium compartment, a volume of transport medium displaced by the swab may displace at least a portion of the air and be contained within the transport medium compartment. In at least one embodiment, the volume of air is about 0.1ml to about 0.2ml. In at least one alternative embodiment, the transport medium compartment contains a volume of transport medium that is equal to or greater than the available volume inside the compartment such that the transport medium also occupies a portion of the tapered portion or mouth of the sample transport medium tube. In such embodiments, when the swab is inserted into the transport medium compartment, the volume of transport medium displaced by the swab will further occupy a portion of the tapered portion or mouth of the sample transport medium tube, and the transport medium compartment will be free of air.

In at least one embodiment, the specimen transport medium tube may be made of plastic, paper, glass, or metallic material, as known in the art, and may be generally cylindrical or prismatic with a circular or polygonal cross-section. In at least one embodiment, the material from which the sample transport medium tube is made may be biodegradable. In at least one embodiment, the sample transport medium tube may include indicia to indicate an estimated volume of liquid content of the tube. For example, markings may be etched or painted on the tube to indicate volume, including but not limited to 0.05ml, 0.1ml, 0.2ml, 0.3ml, 0.4ml, 0.5ml, 0.6ml, 0.7ml, 0.8ml, and 0.9ml.

In at least one embodiment, the specimen transport media tube is intended to be disposable for disposal after a single use. In at least one embodiment, the sample transport medium tube may be reusable. In such embodiments, the used sample transport medium tube may be cleaned and sterilized using procedures well known in the art, including but not limited to autoclaving, irradiation with gamma radiation, and treatment with ethylene oxide, and refilled with transport medium by a user of the sample transport medium tube. In at least one embodiment, clean or unused sample transport medium tubes can be filled with transport medium by a user, and the filled tubes can then be sterilized to simultaneously sterilize the transport medium.

Thus, it is contemplated that the sample transport medium tube of the present invention may be provided for use in a wide variety of embodiments. In at least one embodiment, the transport medium compartment of the sample transport medium tube can be empty so that it can be filled to a desired level with a desired transport medium by a user. In at least one embodiment, the transport medium compartment of the sample transport medium tube can be pre-filled with transport medium by the manufacturer. In at least one embodiment, the sample transport medium tube, including any transport medium contained within the tube, may be pre-sterilized by the manufacturer. In at least one embodiment, the sample transport media tube, whether pre-filled or pre-sterilized, may be pre-packaged by the manufacturer with a swab for collecting the sample. In at least one embodiment, the swab may be pre-sterilized. In at least one embodiment, the swab may be pre-attached to the cap and cap insert of the specimen transport medium tube as described herein. In at least one embodiment, the sample transport medium tube, transport medium, and swab may be provided together by the manufacturer as a kit, which may or may not be pre-sterilized. In at least one embodiment of the kit, the swab may be packaged separately from the sample transport medium tube or may be pre-attached to a tube, which may be pre-filled with transport medium or may be filled with transport medium provided in a separate container within the kit. The kit may further contain instructions for using the components of the kit. Other configurations in which the sample transport medium tube of the present invention may be provided for use will be apparent to those skilled in the art.

Another aspect of the invention provides a method for collecting a swab sample or specimen for laboratory testing including, but not limited to, microbiology, molecular diagnostics, and other examinations. In at least one embodiment, the method includes collecting a sample on a swab tip using a swab comprising a swab handle and a swab tip as described herein. The swab tip is then inserted into the opening of the mouth of the sample transport medium tube as described herein such that the swab tip enters the opening of the transport medium compartment and is immersed in the transport medium contained in the transport medium compartment. The swab handle may optionally be broken at the breaking point or cut at any desired point to form a shortened swab containing a swab tip such that the shortened swab may be contained within the sample transport medium tube.

A cap comprising a cap insert (which comprises a cap insert head) is then secured to the opening of the mouth such that the cap insert head is used to seal the transport medium within the transport medium compartment, as described herein. The shortened swab handle may be completely sealed within the transport medium compartment. Alternatively, the handle of the swab or shortened swab may extend alongside or through the cap insert head into the mouth of the sample transport medium tube, and may optionally be further fastened against or within the cap insert, as described herein. In at least one embodiment, the swab may be attached to the cap or cap insert prior to collecting the sample.

The sample transport medium tube may then be transported to a facility for testing or analyzing the collected sample. In at least one embodiment, to retrieve the sample, the cap and cap insert may be removed from the tube and the swab or shortened swab may be removed and discarded. In embodiments where the swab is attached to a cap or cap insert, removal of the cap and cap insert may also be used to remove the swab. In at least one embodiment, the sample transport medium tube may be agitated prior to removal of the swab or shortened swab to facilitate transfer of the collected sample from the swab tip to the transport medium within the tube. Such agitation may be by shaking, tapping or vibrating a tube containing the swab tip, or by agitating the swab tip within the transport medium. In at least one embodiment, the sample transport medium tube may be agitated with a vortex mixer, as is known in the art. Prior to disposal, the swab tip may be pressed against the side of the sample transport medium tube to express out transport medium trapped in the fibers or pores of the swab tip.

The transport medium containing the collected sample can then be retrieved from the tube for testing. In at least one embodiment, the transport medium containing the collected sample may be retrieved from the transport medium compartment by aspirating or sucking the transport medium containing the collected sample from the tube. In at least one embodiment, a pipette tip attached to a squeeze ball or a commercially available mechanical or electronic pipette may be inserted through an opening in the mouth of the specimen transport medium tube, and transport medium containing the collected specimen may be aspirated into the pipette tip. In at least one embodiment, an elongated pipette tip having an outer diameter in the range of less than 1mm to about 5mm is conveniently used for this purpose, as such pipette tip can be inserted into the full length of the transport medium compartment. Suitable pipette tips include, but are not limited to, pipette tips having a volume of 1-200. Mu.L and a diameter of 0.5mm Gel loading pipette tip, fisherbra with 1-200 μL volume and 0.6mm outer diameternd ^TM Gel loading tips, and other known or commercially available pipette tips having a volume of 200 μl or less. Advantageously, the larger diameter of the mouth of the sample transport medium tube compared to the diameter of the transport medium compartment allows the user to more easily insert the pipette tip into the mouth of the tube.

In at least one embodiment where the specimen transport medium tube includes an opening at the distal end capped with a distal end cap, the transport medium containing the collected specimen may be retrieved from the transport medium compartment by removing the distal end cap and allowing the transport medium containing the collected specimen to drain into a collection container, which may be, for example, a microcentrifuge tube having a volume of 1.5ml or 2ml or a 15ml or 50ml conical tube, as is known in the art. The discharge of the transport medium containing the collected sample into the collection container may be facilitated by, for example, positioning a pipette tip mounted on a mechanical or electronic pipette within the mouth of the tube and depressing the plunger of the pipette, thereby pushing air through the pipette tip into the transport medium compartment and forcing the transport medium into the collection container through an opening at the distal end of the transport medium compartment. Standard pipette tips having a volume of 1ml or 200 μl are conveniently used for this purpose. The swab or shortened swab may be pushed out of the transport medium compartment with the transport medium or may be removed from the transport medium compartment before the transport medium is discharged. The swab tip may be further agitated or stirred within the retrieved shipping medium prior to discarding the removed swab tip to facilitate further transfer of the sample from the swab tip to the shipping medium, and the swab tip may be pressed against the sides of the container containing the shipping medium to express the shipping medium trapped in the fibers or pores of the swab tip.

Advantageously, in at least one embodiment, the swab tip carrying the collected sample during transport in the sample transport medium tube of the present invention may remain submerged in a lower volume of transport medium than in a conventional transport medium tube. In this way, the sample on the swab tip may be diluted to a lesser extent than in conventional transport media tubes, and may be protected from degradation and dehydration during transport. Thus, the use of the sample transport medium tube of the present invention may result in improved detection of low levels of analyte in a sample, for example by quantitative polymerase chain reaction (qPCR) or quantitative reverse transcriptase PCR (qRT PCR) techniques, without requiring changes in the assay protocol or reagent concentration. For example, pooling of samples may be accomplished using samples collected in the sample transport medium tube of the present invention. Alternatively, analysis can be accomplished using samples collected in the sample transport medium tube of the present invention, while avoiding the need for RNA extraction. Thus, test cost and turn-around time can be reduced and throughput increased. In addition, the use of the specimen transport medium tube of the present invention may find wide application in many fields, such as in environmental and industrial settings, where swab samples containing low levels of multiple analytes may be collected.

Description of specific embodiments

Other features of the present application will become apparent from the following non-limiting examples of embodiments which illustrate, by way of example and with reference to the accompanying drawings, the principles of the application.

An embodiment of a sample collection kit according to the present application is shown in fig. 1A. The kit 1 comprises a swab 3 having a swab handle 2 with a breaking point 2a and a swab tip 5. The kit 1 further comprises a sample transport medium tube 17 having a mouth 13a and a transport medium compartment 19 having a reduced diameter compared to the diameter of the mouth 13a and containing a transport medium 20. A tapered portion 18 having a gradually decreasing diameter connects the mouth 13a to the transport medium compartment 19. Cap 9a includes a helical thread 11a on its inner surface which mates with a complementary thread 15a on the outer surface of mouth 13 a. The cap 9a further comprises a cap insert 12 which sits tightly against the inner side wall of the conical portion 18 when the cap 9a is fastened to the mouth 13 a. The distal cap 27 carries a support structure 29 and further includes helical threads that mate with complementary threads 23 on the exterior of the distal end 24 of the sample transport medium tube 17.

In use of the embodiment of fig. 1A, as depicted in fig. 3A-3C, the swab 3 is used to collect a sample, such as an oropharyngeal sample, on the swab tip 5. The swab 3 is then inserted into the sample transport medium tube 17 such that the swab tip 5 is immersed in the transport medium 20 contained in the transport medium compartment 19, as seen in fig. 3B. The swab handle is then broken at the breaking point 2a to provide a shortened swab 3 that can be received within the sample transport medium tube 17, and the cap 9a with the cap insert 12 is attached to the mouth 13a and secured by engagement with the complementary helical threads 11a and 15a such that the cap insert 12 seals the opening of the transport medium compartment 19 and secures the shortened swab 3 within the transport medium compartment 19, as seen in fig. 3C.

Once the specimen transport medium tube 17 has been received in the test facility, the specimen may be retrieved, for example, for testing, as depicted in fig. 4A-4C. Cap 9a is removed from mouth 13a as seen in fig. 4A, and distal cap 27 is removed from distal end 24 of sample transport medium tube 17 as seen in fig. 4B. The pipette tip 25 is inserted into the mouth 13a, and a pipette attached to the pipette tip 25 is used to push air into the transport medium compartment 19 so as to push the transport medium 20 out of the transport medium compartment 19 into the collection container 26, as seen in fig. 4C. The swab 3 may be pushed out of the transport medium compartment 19 into the collection container 26 together with the transport medium 20, or the swab 3 may be removed from the transport medium compartment 19 with forceps, for example before the transport medium 20 is removed from the transport medium compartment 19.

An alternative embodiment of the sample collection kit of the present invention is shown in fig. 1B, wherein cap insert 12 carries an external helical thread 11B that mates with a complementary thread 15B located on the interior of mouth 13B. Another alternative embodiment is shown in fig. 1C, comprising a cap insert 12 having a cap insert head 12g of designed profile that complements the internal profile of the tapered portion 18 so as to form a close fit therewith. The embodiment shown in FIG. 1C also includes an outer sidewall 21 extending to the distal end 24 of the specimen transport media tube 17, providing a support structure for the tube. The outer side wall 21 is open at the distal end 24 allowing easy removal and replacement of the distal cap 27, so that the transport medium compartment 19 is accessible from the distal end 24.

Fig. 2A shows an embodiment of the sample collection kit of the present invention similar to fig. 1A, but wherein the sample transport medium tube 17 has a longer mouth 13a configured such that the sample transport medium tube 17 can accommodate a swab or a shortened swab having a longer net length after breaking at the breaking point, while keeping the volume of the transport medium compartment 19 advantageously low, as discussed above. In this embodiment, the cap insert 12 is conical at the end remote from the cap so as to complement the internal profile of the conical portion 18. The cap insert 12 also carries a cap insert head in the form of an O-ring 12a which fits into the groove 12b and has a length such that the O-ring 12a can be placed tightly against the inner side wall of the tapered portion 18 when the cap 9a is fastened to the mouth 13a of the tube 17. Fig. 2B shows an embodiment similar to fig. 2A but containing an outer sidewall 21, similar to the embodiment of fig. 1C.

In use of the embodiment of fig. 2A, as depicted in fig. 5A to 5D, a swab 3 with a flexible handle 2 is used to collect a sample, such as a nasopharyngeal sample, on the swab tip 5. The swab 3 is then inserted into the sample transport medium tube 17 such that the swab tip 5 is immersed in the transport medium 20 contained in the transport medium compartment 19, as seen in fig. 5B. The swab handle is then broken at the breaking point 2a to provide a shortened swab 3 that can be housed within the sample transport medium tube 17. The flexibility of the swab handle 2 allows the cap 9a and cap insert 12 to be inserted into the sample transport medium tube 17 to move the handle 2 towards the side wall of the tube 17. When the cap 9a is secured to the mouth of the sample transport medium tube 17, the O-ring 12a on the cap insert 12 sits tightly against the sloped side wall of the tube 17, deforming to accommodate the width of the handle 2 and sealing the opening of the transport medium compartment 19, as seen in fig. 5C. When the specimen transport medium tube 17 is received in the test facility, the cap 9a and shortened swab 3 may be removed from the tube and the transport medium 20 containing the sample may be aspirated for analysis using the pipette tip 25.

Fig. 2C shows an alternative embodiment in which the O-ring 12A is attached to a cap insert 12C having a smaller diameter than the cap insert 12 of the embodiment of fig. 2A, thereby reducing the material cost required to manufacture the cap insert while maintaining the ability of the O-ring 12A to sit tightly against the inner side wall of the tapered portion 18. As seen in fig. 2D, cap insert head 12D may have a generally conical shape contoured to seat tightly against the side wall of tapered portion 18. In addition, replacement cap insert head 12e may form a seal within the opening of transport medium compartment 19, allowing cap insert 12f to have an even smaller diameter than cap insert 12 c.

An alternative embodiment of a sample collection kit of the present invention is described with reference to fig. 6A to 6F and 7A to 7C, comprising a sample transport medium tube 17 with an outer side wall 21, cap 31 and cap insert 37 as previously described. Cap 31 contains a helical thread to engage with a complementary helical thread at the mouth 13a of sample transport medium tube 17, as previously described. Cap insert 37 has a first end 35 configured to connect to connector 33 on cap 31. Cap insert 37 also has a second end 38 with a ridge configured to engage with a groove 44 (as seen in fig. 7A) in cap insert head 39 by interlocking or in a tight friction fit. In at least one embodiment, the ridge at the second end is made of a plastic material, including but not limited to polypropylene or polystyrene. The cap insert 37 further contains an internal longitudinal channel 43 configured to closely receive the swab handle 2 of the swab 3. In at least one embodiment, the cap insert 37 is perforated or includes an opening perpendicular to the interior longitudinal channel 43 through which the swab handle 2 is visible when inserted into the interior longitudinal channel 43. As seen in fig. 7A, the cap insert head 39 includes a sealing portion 41, a conical portion 42, and an internal channel 45, similar to the internal longitudinal channel 43 of the cap insert 37, configured to closely receive the swab handle 2 of the swab 3. In at least one embodiment, the diameter of the sealing portion 41 is greater than the maximum inner diameter of the tapered portion 18 of the sample transport medium tube 17. In at least one embodiment, the diameter of conical portion 42 is greater than the inner diameter of the corresponding point on conical portion 18.

In use, as seen in fig. 6A, 6B and 6C, the swab 3 is used to collect a sample on the swab tip 5, and the swab handle 2 is inserted into the internal channel 45 (seen in fig. 7A) of the cap insert head 39 and the internal longitudinal channel 43 of the cap insert 37 until the breaking point 2a on the swab handle 2 passes through the length of the internal longitudinal channel 43 and occurs at the first end 35 of the cap insert 37. The swab 3 and cap insert 37 are then inserted into the sample transport medium tube 17 such that the swab tip 5 is submerged in the transport medium 20 in the transport medium compartment 19, as seen in fig. 6D. The swab handle 2 is then broken at the breaking point 2a such that the shortened length of the swab 3 is accommodated within the sample transport medium tube 17, as seen in fig. 6E. In an alternative embodiment, the swab 3 may be pre-inserted into the cap insert 37 by the user of the sample collection kit or by the manufacturer of the kit before the swab is used to collect a sample.

When the cap 31 is engaged with the mouth of the tube 17, the connector 33 engages the first end 35 of the cap insert 37 with a snap-fit connection (christofer M Shi Like (Christopher M. Schlick) (10 th 2009) product design methods and practices (Product Design Methods and Practices) CRC Press (CRC Press), pages 172-ISBN 978-0-8247-7565-0) as known in the art for use with the first end of the cap insert 37. Once the connector 33 has engaged the first end 35 of the cap insert 37 to connect the cap 31 to the cap insert 37, removal of the cap 31 from the sample transport medium tube 17 will also serve to remove the cap insert 37 and shortened swab 3 from the sample transport medium tube 17, thereby facilitating removal of the transport medium containing the sample from the sample transport medium tube 17.

In at least one embodiment, the diameter of the sealing portion 41 is greater than the maximum inner diameter of the tapered portion 18 of the sample transport medium tube 17 by, for example, about 2% to about 15%. In at least one embodiment, the diameter of conical portion 42 at any given point is greater than the inner diameter of a corresponding point on the inner sidewall of conical portion 18, for example, from about 2% to about 15%. Thus, when the cap 31 is screwed onto the mouth of the sample transport medium tube 17, the cap insert 37 is further inserted into the sample transport medium tube 17, resiliently compressing and tightly seating the sealing portion 41 of the cap insert head 39 against the inner side wall of the tapered portion 18 of the sample transport medium tube 17, thereby sealing the transport medium 20 within the transport medium compartment 19. Furthermore, as depicted in fig. 7B and 7C, the compression of the cap insert head 39 also compresses the internal channel 45 around the swab handle 2 such that the material of the cap insert head 39 seals tightly to the swab handle 2, thereby preventing any loss of transport medium 20 through the internal channel 45.

Another alternative embodiment of a sample collection kit of the present invention is described with reference to fig. 8A to 8E and 9A to 9C, comprising a sample transport medium tube 17 having an outer side wall 21, cap 51 and cap insert 52 as previously described. The cap 51 and cap insert 52 may be unitary in construction, or may be two separate pieces that are assembled and secured together, for example, during manufacture of the sample collection kit. The cap insert 52 includes a securing clip 53 configured to receive and retain the flexible swab handle 2. Cap insert 52 also includes a cap insert head 55, which, as further seen in fig. 9A, includes a sealing portion 56 and a conical portion 58, and is similar to cap insert head 39 of fig. 6A-6F. The cap insert head 55 may be attached to the cap insert 52 by inserting the ridge 54 on the cap insert 52 into the groove 59 (seen in fig. 9A) of the cap insert head 55. However, cap insert head 55 includes a longitudinal slit 57 instead of an internal channel. In at least one embodiment, the cap insert head 55 may include more than one longitudinal slit. In at least one embodiment, the one or more longitudinal slits extend radially from the edge of the sealing portion 56 toward the interior of the cap insert head 55 a distance no greater than half the radius of the cap insert head 55. In at least one embodiment, the one or more longitudinal slits extend radially from the edge of the sealing portion 56 toward the interior of the cap insert head 55 a distance no greater than one third of the radius of the cap insert head 55. In this way, the ridge 54 on the cap insert 52 may be securely retained in the groove 59 of the cap insert head 55.

In use, as seen in fig. 8B, the swab 3 is used to collect a sample on the swab tip 5 and the swab handle 2 is broken at the breaking point 2a so that the shortened length of the swab 3 can be accommodated within the sample transport medium tube 17, as seen in fig. 8B. The flexible swab handle 2 is then inserted into the longitudinal slit 57 and into the fixing card 53, as seen in fig. 8C. When the cap insert head includes more than one longitudinal slit, insertion of the swab handle 2 into the longitudinal slit 57 is facilitated due to the increased flexibility of the sealing portion 56. Because the swab handle 2 is attached to the cap 51 and cap insert 52 by its insertion into the longitudinal slit 57 and the securing card 53, removal of the cap 51 from the sample transport medium tube 17 will also serve to remove the cap insert 52 and shortened swab 3 from the sample transport medium tube 17, thereby facilitating removal of the transport medium containing the sample from the sample transport medium tube 17.

The shortened swab 3 and cap insert 52 are then inserted into the sample transport medium tube 17 such that the swab tip 5 is submerged in the transport medium 20 in the transport medium compartment 19, as seen in fig. 8D. The cap 51 is secured to the mouth of the sample transport medium tube 17 for further insertion of the cap insert 52 into the sample transport medium tube 17, resiliently compressing and tightly seating the sealing portion 56 of the cap insert head 55 against the inner side wall of the tapered portion 18 of the sample transport medium tube 17, thereby sealing the transport medium 20 within the transport medium compartment 19, as seen in fig. 8E. Furthermore, as depicted in fig. 9B and 9C, the compression of the cap insert head 55 also compresses the longitudinal slit 57 around the swab handle 2 such that the material of the cap insert head 55 is tightly sealed to the swab handle 2, thereby preventing any loss of transport medium 20 through the longitudinal slit 57. Thus, in at least one embodiment, the diameter of the sealing portion 56 is greater than the maximum inner diameter of the tapered portion 18 of the sample transport medium tube 17, for example, by about 2% to about 15%. In at least one embodiment, the diameter of conical portion 58 at any given point is greater than the inner diameter of a corresponding point on the inner side wall of conical portion 18, for example, from about 2% to about 15%.

Examples

Other features of the present invention will become apparent from the following non-limiting examples which illustrate the principles of the invention.

Example 1:

comparative test of leakage and swab submersion in transport Medium

The sample transport medium tube of one unit as described herein is opened by screwing open the cap. The nasopharyngeal swab is retrieved by opening the swab package. The swab stick is shortened by breaking the stick at the breaking point. A swab with a shortened swab stick (net swab stick) was placed in the sample transport medium tube and the transport medium compartment was filled with 0.3ml of blue food color solution. The cap pre-assembled with the cap insert is placed back onto the tube and the cap is screwed onto the tube.

It was observed that the cap insert head not only surrounded the swab stick against the swab, but also contacted the tapered portion of the tube such that the sealing of the liquid within the transport medium compartment was complete. It was further observed that the swab in the sample transport medium tube was completely submerged in the transport medium when inverted. In contrast, when placed in a conventional shipping medium tube (disposable sampler, 10mL vial, commercially available from foresight technologies, inc. (NEST Biotechnology co., ltd), catalog No. 202092) filled with 0.3mL of dye solution, the swab is not completely submerged in the shipping medium prior to tube inversion. The swab in the control tube was not submerged when the tube was inverted. The sample transport medium tube of the present invention ensures that the swab is always submerged in the transport medium and no leakage of liquid from the transport medium compartment of the tube to the main compartment of the tube is observed. This seal and no leakage was observed to last for 5 days even with the tube inverted.

Example 2:

comparative testing of analyte concentration in transport Medium

Eighteen sample transport medium tubes as described herein and 18 conventional tubes were each filled with transport medium (non-inactivating medium based on Hank's balanced salts, 0.3ml for the sample transport medium tube of the present invention and 3ml for the conventional tube). Each of the 36 swabs was individually immersed in a labeled mock sample containing SARS-CoV-2RNA (COVID-19 viral RNA). Each of the 18 impregnated swabs was then placed into a separate sample transport medium tube of the present invention; each of the other 18 swabs was placed into a separate conventional tube. An aliquot of 100 μl of the transport medium was removed from each of the 36 tubes, heated, and then tested in dual SARS-CoV-2 quantitative reverse transcription PCR. Dual SARS-CoV-2 quantitative reverse transcription PCR the 2 regions (N1 and N2 regions) of the viral SARS-CoV-2RNA were tested to further verify the analysis results. The Cq values from quantitative reverse transcription PCR are shown in table 5 below.

Table 5: cq results of N1 and N2 genes from samples collected in conventional tubes and the inventive sample transport media tube

Note that: * Cq values of >37 are excluded from the calculation of average Cq and CV.

^◆ NaN-was not detected.

* CV calculation excludes outliers of 36.4 in this group.

As can be seen from the results shown in Table 5, the average Cq value of the N1 gene quantitative (real-time) PCR of the sample transport medium tube of the present invention was 29.6, which was 3.1 smaller than the average Cq value (average Cq 32.7) of the conventional tube. Since Cq is a direct reflection of the analyte concentration, this difference corresponds to a 8.5-fold higher viral RNA analyte concentration in the sample transport medium tube of the present invention than in conventional tubes. The difference in average Cq value of the N2 gene between the two sets of tubes was 4.7 (average Cq for the conventional tube was 35.5 and average Cq for the inventive sample transport medium tube was 30.9), corresponding to a 25-fold viral RNA analyte concentration in the inventive sample transport medium tube compared to the conventional tube. The results from both the N1 and N2 regions indicate that higher viral RNA analyte concentrations are found in the transport medium contained in the sample transport medium tube of the present invention, reflecting a reduced volume of transport medium in the sample transport medium tube of the present invention compared to that in conventional tubes.

Since the volume of the transport medium is 0.3ml for the sample transport medium tube of the present invention and 3ml for the conventional tube, the analyte concentration of the sample eluted from the swab into the transport medium in the sample transport medium tube of the present invention is expected to be 10 times higher than in the conventional tube. For the N2 test, a greater than 10-fold increase in viral RNA analyte concentration was observed, possibly due to the expected inherent greater error when the Cq value was close to 37.

In addition, it was observed that in the conventional tube set, the presence of viral RNA was not detected in 5 of 18 samples, whereas the presence of viral RNA was detected in all 18 samples from the specimen transport medium tube of the present invention. Thus, from the results of this study, it can be concluded that the detection of low concentration analytes in a sample is significantly improved by using the sample transport medium tube of the present invention.

Example 3:

comparison test of nasopharyngeal swab samples

Twenty previously tested and anonymized nasopharyngeal swab samples obtained during the covd-19 test, which have been stored in universal transport medium (UTM; hanks balanced salt, non-inactivating) at-80 ℃ in a freezer, were used in this study. The local research ethics committee was obtained for review and approval prior to the study. Based on the initial SARS-CoV-2N gene test results, 7 samples have Cq values <25, 6 samples have Cq values of 25-30, 6 samples have Cq values of 30-35, and 1 sample has Cq value of 35-40.

A0.1 mL aliquot of these 20 samples previously found positive for SARS-CoV-2 gene was added to each of the sample transport medium tube of the present invention containing 0.3mL UTM and the paired control Virus Transport Medium (VTM) tube containing 3mL UTM to provide two groups of 20 tubes each. The UTM containing the sample in each tube was then retrieved and passed through KingFisher using the kit supplied by Sieimer's femto ^TM The nucleic acid isolation system (sameimer's femal) performs viral RNA extraction and quantitative reverse transcription PCR testing. Due toDilution and loss of viral titer due to freeze-thawing process, some positive samples were expected to become undetectable in this study. The results are shown in tables 6 to 9 below.

Table 6: detection of patient samples in sample transport Medium tubes and control tubes of the invention Using the SARS-CoV-2N Gene and the ORF1ab Gene

Note that: ND-not detected.

Table 7: positive quantity and detection sensitivity of sample-carrying Medium tube and control tube set of the present invention Using SARS-CoV-2N Gene and ORF1ab Gene

Table 8: detection of patient samples in sample transport Medium tubes and control tubes of the invention Using the E Gene, RDRP and human ribonuclease P test

Note that: ND-not detected.

Table 9: positive numbers and detection sensitivity of sample transport Medium tubes and control groups of the invention Using the SARS-CoV-2E Gene, RDRP and human ribonuclease P test

The results (tables 6 and 8) show that the Cq values of the five gene markers tested for the sample delivery medium tube of the present invention were lower than the Cq values of the control tube, as expected. Notably, the expected difference in dilution factor (0.1 mL diluted to 0.4mL or 0.1mL diluted to 3.1 mL) was 7.75-fold, which corresponds to a Cq difference of 2.95. Thus, the observed Cq differences between the two types of tubes are consistent with this expected difference.

Tables 7 and 9 show the detection sensitivity values for all five genes. The sensitivity clearly shows a better value with the sample of the invention carrying the medium tube than with the control tube, with a sensitivity gain of about 10%.

In summary, in this example, the sample delivery media tube sets of the present invention exhibited consistently better (lower) Cq values than the control. The lower Cq value is associated with better detection sensitivity in the samples prepared in the sample transport medium tube of the present invention compared to the samples prepared in the control tube.

As used herein, the term "about" or "approximately" when applied to a value or range of values means that the value, given the measured property or accuracy, can vary within an acceptable degree of error of the measured quantity such that the deviation is considered equivalent to the value in the art and provides the same function or result. For example, as understood in the art, the degree of error can be represented by the number of significant digits provided for measurement, and includes, but is not limited to, deviations of 1 from the most accurate significant digit reported for measurement. Typical exemplary error levels are within 20 percent (%) of a given value or range of values, preferably within 10%, and more preferably within 5%. Alternatively, and especially in biological systems, the terms "about" and "approximately" may refer to values within an order of magnitude, preferably within 5 times, and more preferably within 2 times the given value. Unless otherwise indicated, the numerical quantities given herein are approximations, by the term "about" or "about" that can be inferred when not explicitly stated.

As used herein, the term "substantially" refers to a complete or nearly complete range or degree of action, feature, characteristic, state, structure, item, or result. For example, another number of values that have a value that is "substantially" equal to one number has such nearly the same value within an acceptable degree of error that the number provides the same function or result. The precise degree of tolerance with respect to absolute integrity may in some cases depend on the particular situation. In general, however, near-complete will have the same overall result as absolute and complete.

The use of "substantially" is equally applicable when used in a negative connotation, meaning that the effect, feature, characteristic, state, structure, item, or result is completely or nearly completely absent. For example, a composition that is "substantially free" of an ingredient or element will be completely devoid of that ingredient or element, or so nearly completely devoid of that ingredient or element that the effect will be the same as it is completely devoid of that ingredient or element. In other words, a composition that is "substantially free" of an ingredient or element may still actually contain such items, so long as there is no measurable or significant effect.

As used herein, terms indicating relative directions or orientations, including, but not limited to, "upper," "lower," "top," "bottom," "vertical," "horizontal," "outer," "inner," "front," "rear," and the like are intended to aid in the description of the invention by indicating relative orientations or directions in general use, and are not intended to limit the scope of the invention in any way to such orientations or directions.

The examples described herein are intended to illustrate the compositions and methods of the present invention and are not intended to limit the scope of the invention. It is intended to include various modifications and alterations consistent with the entire specification and apparent to those skilled in the art. The following claims should not be limited to the specific embodiments set forth in the examples, but should be given the broadest interpretation consistent with the description as a whole.

Claims

1. A specimen transport media tube for transporting a specimen disposed on a swab tip of a swab, the specimen transport media tube comprising:

a mouth end comprising an opening configured to receive the swab tip;

a cap configured to engage with the mouth end so as to seal the opening, the cap comprising a cap insert;

A distal end opposite the mouth end and defining a longitudinal axis with the mouth end; and

at least one sidewall extending longitudinally between the mouth end and the distal end to define and enclose an interior space within the specimen transport medium tube;

wherein the interior space is in fluid communication with the opening of the mouth end, and wherein the interior space comprises:

a mouth located at the mouth end, the mouth having an inner diameter thereof;

a transport medium compartment longitudinally aligned with the longitudinal axis and configured to hold a transport medium and the swab tip, the transport medium compartment having an inner diameter thereof and an internal volume thereof, wherein the inner diameter of the transport medium compartment is less than the inner diameter of the mouth and less than or equal to 10mm, and the internal volume of the transport medium compartment is less than 1ml; and

a tapered portion disposed between the mouth and the transport medium compartment, wherein the tapered portion is in fluid communication with the mouth and the transport medium compartment and is configured to allow unimpeded passage of the swab tip from the opening at the mouth end to the transport medium compartment;

Wherein the inner diameter of the tapered portion decreases from the inner diameter of the mouth at the junction between the tapered portion and the mouth to the inner diameter of the transport medium compartment at the junction between the tapered portion and the transport medium compartment;

wherein the cap insert is configured to prevent fluid communication between the mouth and the transport medium compartment when the cap is engaged with the mouth.

2. The specimen transport media tube of claim 1, wherein the distal end comprises a distal end opening in fluid communication with the transport media compartment, and wherein the specimen transport media tube further comprises a distal cap configured to engage the distal end so as to seal the distal end opening.

3. The specimen transport media tube of claim 1, wherein the distal end comprises a distal wall vertically aligned with and integral with one or more side walls.

4. The specimen transport media tube of any of claims 1-3, further comprising a support structure configured to stably support the specimen transport media tube stationary on the distal end of the specimen transport media tube.

5. The specimen transport media tube of any one of claims 1-4, further comprising one or more outer side walls longitudinally aligned with the longitudinal axis and external to at least the one or more side walls at the tapered portion and at the transport media compartment.

6. The specimen transport media tube of claim 5, wherein the specimen transport media tube is configured for use in an automated liquid handling system.

7. The specimen transport media tube of any of claims 1-6, wherein the cap insert is configured to engage with a handle of the swab.

8. The specimen transport medium tube of any one of claims 1-7, further comprising the transport medium within the transport medium compartment.

9. The specimen transport medium tube of any one of claims 1-8, wherein the inner diameter of the transport medium compartment is less than or equal to 8mm.

10. The specimen transport medium tube of any one of claims 1-8, wherein the inner diameter of the transport medium compartment is less than or equal to 5mm.

11. The specimen transport medium tube of any one of claims 1-10, wherein the internal volume of the transport medium compartment is less than or equal to 0.8ml.

12. The specimen transport medium tube of any one of claims 1-10, wherein the internal volume of the transport medium compartment is less than or equal to 0.5ml.

13. The specimen transport media tube of any one of claims 1-12, wherein the cap insert forms a seal against the one or more sidewalls of the tapered portion when the cap is engaged with the interface.

14. A sample collection kit comprising a swab; transporting the medium; and a specimen transport medium tube according to any one of claims 1 to 13.

15. The sample collection kit of claim 14, further comprising instructions for use of the kit.

16. The sample collection kit of claim 14 or 15, wherein the transport medium is contained in the transport medium compartment of the sample transport medium tube.

17. The specimen collection kit of any one of claims 14 to 16, wherein the swab is attached to the cap of the specimen transport media tube.

18. The sample collection kit of any one of claims 14 to 17, wherein the swab is a nasopharyngeal swab.

19. The sample collection kit of any one of claims 14 to 17, wherein the swab is an oropharyngeal swab.