WO2022187609A2

WO2022187609A2 - Fluid handling device for a biological container

Info

Publication number: WO2022187609A2
Application number: PCT/US2022/018890
Authority: WO
Inventors: Emily Rose KOHLER; Collin Tyler MASON; Jeff LOU
Original assignee: Ginkgo Bioworks, Inc.
Priority date: 2021-03-04
Filing date: 2022-03-04
Publication date: 2022-09-09
Also published as: WO2022187609A9

Abstract

An apparatus and corresponding method of handling fluid in a sample container is provided in which the sample container includes a plurality of carriers (e.g., swabs) with a sample (e.g., a biological or chemical sample) and a fluid. An insert having a sidewall with an internal channel defined therein is placed within the container which displaces (e.g., radially displaces) the carrier within the container such that the internal channel of the insert is free of any carriers. The proximal end of the inset sealing engages the sample container rim, and can receive a pipette for removing/adding fluid within the container through the internal channel of the insert.

Description

FLUID HANDLING DEVICE FOR A BIOLOGICAL CONTAINER

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority under 35 Ci.S.C. § 119(e) of U.S.

Provisional Application No. 63/156,592 filed March 4, 2021, the entire contents of which are hereby incorporated by reference.

BACKGROUND OF THE DISCLOSED SUBJECT MATTER

Field of the Disclosed Subject Matter

[0002] The disclosed subject matter relates to a system for accessing a sample and handling fluid comprising the sample within the container. Particularly, the disclosed subject matter is directed to rapidly and reliably extracting a sample(s) from multiple sample carriers (e.g. swabs), as well as transportation and/or storage thereof.

Description of Related Art

[0003] Biological specimens or samples are needed for a variety of medical treatments, e.g. , the prediction or diagnosis of disease in a subject, and devices for obtaining a sample typically allow only a single swab to be used per subject, which limits efficiency of processing and delays results. Bulk or batch processing is required to rapidly process large numbers of samples, however, numerous challenges exist with this approach, including the pipette colliding with swabs within a sample container, a undesirably high force requirement to drive the pipette through the swabs, and clogging of the pipette tip due to pieces of the swabs breaking off due to the frictional forces exerted by the insertion step. Additionally, the pipette can collide with the swabs as it is inserted within the container, tensioning the swabs, which can result in swabs springing loose upon removal of the pipette thereby contaminating the biological sample and exposing personnel to potentially hazardous conditions. These risks can be exacerbated with the use of robotic pipette systems that automatically carry out the insertion step irrespective of swab positioning.

[0004] There thus remains a need for a safe and efficient system for handling containers with multiple carriers that can reliably remove fluid within the container to access the biological samples within the carriers, without interfering with the carriers themselves. The device and methods disclosed herein can further increase pooled testing capacity by the usage of high-throughput, parallel-processing robotic liquid handlers.

SUMMARY OF THE DISCLOSED SUBJECT MATTER [0005] The purpose and advantages of the disclosed subject matter will be set forth in and apparent from the description that follows, as well as will be learned by practice of the disclosed subject matter. Additional advantages of the disclosed subject matter will be realized and attained by the methods and systems particularly pointed out in the written description and claims hereof, as well as from the appended drawings.

[0006] To achieve these and other advantages and in accordance with the purpose of the disclosed subject matter, as embodied and broadly described, the disclosed subject matter includes a device for handling fluid in a sample container having an open proximal end and a closed distal end, the container configured to receive at least one carrier carrying a fluid having a sample therein. The device comprises an insert having a proximal end and a distal end, the insert configured to be coupled to the container and having: a first sidewall defining a first diameter at the proximal end, a second sidewall defining a second diameter at the proximal end, and a third sidewall defining an internal channel which is open at the proximal end and has at least one opening at the distal end, such that when the device is inserted into the container, the first and/or second sidewall contact the proximal end of the container, and the internal channel configured to receive a pipette, with the pipette in fluid communication with the fluid within the container. Additionally, when the device is inserted into the container, the internal channel of the insert is free of the carrier(s) ( e.g ., swabs).

[0007] In some embodiments, the disclosure provides: a device for handling fluid in a sample container having an open proximal end and a closed distal end, the sample container being configured to receive a fluid and at least one carrier carrying a sample, wherein the fluid can be in fluid communication with the sample, the device comprising: an insert having a proximal end and a distal end, the insert being configured to be coupled to the sample container and having: a first sidewall defining a first diameter at the proximal end, a second sidewall defining a second diameter at the proximal end, and a third sidewall defining an internal channel which is open at the proximal end and has at least one opening at or near the distal end, such that when the device is inserted into the sample container, the first and/or second sidewall contact the proximal end of the sample container, and wherein: the internal channel is configured to receive a pipette comprising an orifice, wherein the orifice can be in fluid communication with the fluid within the sample container.

[0008] In some embodiments, the third sidewall of the insert is frustoconical.

[0009] In some embodiments, the proximal end of the container is threaded and the insert is removably coupled to the container via a threaded connection.

[0010] Also, the device can include a cap configured to seal the opening in the proximal end of the insert, e.g ., the cap can be removably coupled to the insert via a threaded connection or snap-fit, and/or can be tethered to the container via a flexible connector.

[0011] In some embodiments, the insert further comprises a pierceable upper surface which seals the proximal end of the insert (e.g., a foil seal).

[0012] In some embodiments, at least one of the first sidewall or second sidewall of the insert engages the proximal end of the container to concentrically align the insert with the container.

[0013] In accordance with another aspect of the disclosure, a device for handling fluid in a sample container having an open proximal end and a closed distal end is provided, wherein the container is configured to receive at least one carrier (e.g. swabs) with a fluid having a biological sample therein. The device comprises an insert, the insert removably coupled to the proximal end of the container and having: a first diameter at a proximal end, a second diameter at a distal end, and a sidewall defining an internal channel in fluid communication with the fluid within the container; wherein placement of the insert within the container displaces the carrier(s) with the internal channel remaining free of the carrier(s). [0014] In some embodiments, at least one opening in the insert sidewall is disposed between proximal and distal ends thereof.

[0015] In some embodiments, the insert has a tapered sidewall.

[0016] In some embodiments, the proximal end of the insert includes a sealing ring, the sealing ring configured to engage the proximal end of the container.

[0017] In some embodiments, the sealing ring engages an interior surface and an exterior surface of the container.

[0018] In some embodiments, the sealing ring concentrically aligns the insert with the container.

[0019] In some embodiments, a cap is also included with the cap configured to releasably seal the opening in the proximal end of the device via a threaded connection or a snap-fit connection, and/or the cap can be tethered to the container and/or the device. [0020] In accordance with another aspect of the disclosure, a method of handling fluid in a sample container comprises: providing a container having a central longitudinal axis, the container including at least one swab with a biological sample, and a fluid; placing an insert within the container, the insert having: a first diameter at a proximal end, a second diameter at a distal end, and a sidewall defining an internal channel in fluid communication with the fluid within the container. Placement of the insert within the container radially displaces the swab(s) within the container, and a pipette is placed at least partially within the internal channel of the insert to remove or add fluid disposed within the container through the internal channel of the insert. In some embodiments, at least one of the steps of placing an insert, placing a pipette, or removing or adding fluid is performed by a machine or robot and/or is a step in an automated or partially automated process.

[0021] In some embodiments, placing the insert within the container includes engaging an interior surface of the container and an exterior surface of the container with a portion of the insert.

[0022] In some embodiments, the pipette remains spaced from the swab(s) during fluid removal.

[0023] In some embodiments, the internal channel of the insert is aligned with the central longitudinal axis of the container.

[0024] In some embodiments, displacement of the swab(s) includes distributing the swabs evenly around the central longitudinal axis of the container.

[0025] In some embodiments, the pipette includes an orifice at a distal end thereof, the pipette orifice disposed at a location spaced from the distal end of the insert.

[0026] In some embodiments, the pipette orifice is disposed at a location spaced from at least one opening in the insert sidewall.

[0027] In some embodiments, the method also includes dispensing fluid from the pipette into the container.

[0028] In some embodiments, removing fluid includes automatically positioning at least one pipette above the container, e.g., by positioning a plurality of pipettes above a plurality of containers with a robotic armature. In some embodiments, the at least one pipette is automatically displaced downward a predetermined depth into the container.

[0029] It is to be understood that both the foregoing general description and the following detailed description are exemplary and are intended to provide further explanation of the disclosed subject matter claimed. [0030] The accompanying drawings, which are incorporated in and constitute part of this specification, are included to illustrate and provide a further understanding of the method and system of the disclosed subject matter. Together with the description, the drawings serve to explain the principles of the disclosed subject matter.

BRIEF DESCRIPTION OF THE DRAWINGS [0001] A detailed description of various aspects, features, and embodiments of the subject matter described herein is provided with reference to the accompanying drawings, which are briefly described below. The drawings are illustrative and are not necessarily drawn to scale, with some components and features being exaggerated for clarity. The drawings illustrate various aspects and features of the present subject matter and may illustrate one or more embodiment(s) or example(s) of the present subject matter in whole or in part.

[0031] FIG. 1 is an illustration of pooled sample swabs, approximately 20-30 count, in 50mL cylindroconical sample containers, in accordance with the disclosed subject matter. [0032] FIG. 2 is an illustration of a series of pipettes inserted within the containers disclosed in Fig. 1, in accordance with the disclosed subject matter.

[0033] FIG. 3 is a schematic representation of an exemplary insert disposed within the sample container, in accordance with the disclosed subject matter.

[0034] FIGS. 4A-F are schematic, cross-sectional, representations of exemplary embodiments of inserts for placement within a sample container, in accordance with the disclosed subject matter.

[0035] FIGS. 5A-B are schematic representations of exemplary embodiments of inserts for placement within a sample container, in accordance with the disclosed subject matter.

[0036] FIGS. 6A-C are schematic representations of exemplary embodiments of inserts for placement within a sample container, in accordance with the disclosed subject matter. FIG. 6A is a top view an exemplary insert; FIG. 6B is a side view of an exemplary insert; FIG. 6C is a perspective view of an exemplary insert.

[0037] FIG. 7 is a cross-sectional view, taken along plane A-A, of the exemplary insert shown in Fig. 6A, in accordance with the disclosed subject matter.

[0038] FIG. 8 is a schematic representation of a cap that can be employed with the device disclosed herein, in accordance with the disclosed subject matter. [0039] FIG. 9 is a schematic representation of exemplary embodiment of the device, with the carriers, insert and pipette disposed within the container, in accordance with the disclosed subject matter.

[0040] FIGS. 10-12 are schematic representations of exemplary embodiments of the device, with the carriers, insert and pipette disposed within the container, in accordance with the disclosed subject matter.

[0041] FIGS. 13A-D are schematic representations of another aspect of the present disclosure, including a removable cap sized to engage the container and collect a predetermined dosage of fluid.

[0042] FIG. 14 is a schematic representation of another aspect of the present disclosure, including a puncturable sample container, where contents of the container can be accessed upon piercing the container wall.

DETAILED DESCRIPTION OF AN EXEMPLARY EMBODIMENT [0043] Reference will now be made in detail to exemplary embodiments of the disclosed subject matter, an example of which is illustrated in the accompanying drawings. The method and corresponding steps of the disclosed subject matter will be described in conjunction with the detailed description of the system.

[0044] The methods and systems presented herein may be used for collection of samples (e.g., chemical or biological samples) and allows for rapid processing and bulk handling of multiple carriers within a single container. In the exemplary embodiments illustrated, the carrier containing the biological sample is shown as a medical swab (e.g., anterior nares swabs), but alternative carriers can be employed within the scope of the present disclosure.

[0045] Throughout this disclosure, the term “sample,” “test sample,” “specimen,”

“biological sample,” “biological specimen,” “sample from a subject,” or “subject sample” are used interchangeably, and refer to a sample or isolate of tissue or cell(s) that can be used directly as obtained from a subject or can be pre-treated, such as by filtration, distillation, extraction, concentration, centrifugation, inactivation of interfering components, addition of reagents, addition of stabilizers, liquification, sonication, vortexing, mixing, dilution, fragmentation, aliquoting, and the like, to modify the character of the sample in some manner as known in the art. The sample may be any tissue or cell sample taken or derived from the subject. In some embodiments, the sample from the subject may comprise protein, nucleic acid (e.g, RNA and/or DNA), lipid, and/or polysaccharide. Any cell type, tissue, or bodily fluid may be utilized to obtain a sample. The tissue may be, for example, but is not limited to, cheek tissue, tongue tissue, nasal tissue, skin tissue, throat tissue, rectal tissue, vaginal tissue, cervical tissue, or any other tissue obtainable by contact with a swab or the like. The bodily fluid may be, for example, but not limited to, blood drops or spatter, saliva, urine, mucus, or any other bodily fluid obtainable by contact with a swab or the like. While the exemplary embodiments illustrated herein are directed towards health care applications, the present disclosure also extends to myriad other applications, e.g., environmental or industrial sampling including cleanroom sampling, outdoor sampling, forensic sampling, etc. Likewise, the sampling described in the exemplary embodiments is biological, but the present disclosure also extends to a variety of other types of samples, such as chemical samples or toxic samples (e.g., samples comprising or suspected to comprising any of: radioactive materials, halogenated compounds, pollutants, environmental pollutants, hazardous compounds, etc.).

[0046] The term also means any biological material being tested for and/or suspected of containing an analyte of interest, for example, but not limited to, DNA, RNA, protein(s), lipid(s), antibodies, antigens, modified proteins (e.g, glycosylated, phosphorylated, ubiquitinated, sumolyated, and other modifications known in the art), or other cellular components that can be used to measure and provide diagnostic avenues for predicting or diagnosing any disease or condition of a subject in need thereof. The sample can comprise further moieties in addition to the analyte of interest such as antibodies, antigens, haptens, hormones, drugs, enzymes, receptors, proteins, peptides, polypeptides, oligonucleotides, or polynucleotides. Additionally or alternatively, the sample can include chemical samples which can be collected, for purpose of illustration and not limitation, on carriers that are eluted with a diluent.

[0047] The term “subject” or “patient” as used herein interchangeably means any vertebrate. In some embodiments, the subject or patient may be a human or non-human. The subject or patient may or may not be undergoing treatment for a disease. In some embodiments, the subject or patient may be a human subject at risk for developing or already having a disease.

[0048] As illustrated in Fig. 1, a plurality of swabs 10 can be housed within a graduated sample container 100 In the exemplary embodiments shown herein, the container has a 50 mL volume and houses approximately 20-30 swabs, but alternative capacities are within the scope of the present disclosure. Figure 2 depicts an automated liquid handling system where a plurality of pipettes 400 extend downwardly from a robotic armature that can be programmed to move into alignment with the underlying containers. The pipettes can then be simultaneously displaced downwardly a predetermined depth for insertion into the opening of containers 100 - e.g. , until orifices of the pipettes (disposed at the distal end thereof) is submerged below the fluid medium or sample solution (e.g., a fluid comprising a sample) within the sample container. A variety of solution compositions can be employed with the present disclosure, including for purpose of illustration and not limitation, those comprising a diluent such as water or saline or phosphate buffered saline, which serve to release the analyte from the carrier.

[0049] As noted above, automated liquid handling of containers housing multiple swabs presents risk due to cross-contamination events (e.g., caused by rapid swab ejection during a collision or surface adhesion of a swab to the pipette tip). These systems also lack reliability in liquid transfer accuracy due to geometry alteration of the pipette tip during collision, physical obstruction of pipette tip orifice, or automated abortion of the robot control method under a fault scenario. Additionally, this approach can lead to increased wear on automated liquid handlers due to non-typical operational forces encountered in swab shaft collision.

[0050] Accordingly, the present disclosure provides an insert device for placement within the sample container 100 that prevents the multiple swabs contained therein from occluding, contacting or otherwise interfering with the insertion and operation of the pipettes. Thus the present disclosure increases pooled testing capacity by the usage of high- throughput, parallel-processing robotic liquid handlers (e.g. pipettes).

[0051] For purpose of explanation and illustration, and not limitation, an exemplary embodiment of the system in accordance with the disclosed subject matter is shown in Fig. 3 and is designated generally by reference character 200. Similar reference numerals (differentiated by the leading numeral) may be provided among the various views and Figures presented herein to denote functionally corresponding, but not necessarily identical structures.

[0052] As shown in Fig. 3, the system generally includes a sample container 100 configured as a cylindroconical tube that has a height A, with an open proximal end having a first diameter B, and a closed distal end C with a tapered portion D (having a smaller diameter). A unique identifier for tracking and sample retrieval process can be included (e.g. affixed to the exterior of the container, and/or a closure cap). The unique identifier can be a bar code, a QR code, or any of several encoded symbols which when scanned can identify the container 100. The tube can also include a graduated scale on the sidewall, and be made of a variety of (transparent, translucent or opaque) materials ( e.g ., glass, plastic, polymer, metal, etc.) that exhibit the desired strength and chemical properties (e.g. inert) as suited for the particular biological sample to be housed therein.

[0053] As shown in Fig. 3, the insert 200 can be placed within the container 100 with a proximal end of the insert 200 coinciding in location with the proximal end, or mouth, of the container 100. The insert 200 is concentrically aligned with the container 100 such that a central longitudinal axis of the insert is aligned with a central longitudinal axis of the container. (For clarity, the swabs are omitted from view in Fig. 3, but are illustrated in Fig.

9). In the exemplary embodiment shown, the inset 200 has a first diameter at its proximal end and a second (e.g. smaller) diameter at its distal end. In some embodiments, the difference in diameter can be a gradual taper (e.g, frustoconical), such that the exterior surface of the insert 200 has a smooth, contiguous, surface free of any abrupt angles or edges. Such a design can be advantageous in that it minimizes the risk of snagging swabs disposed within the container 100 upon insertion of the insert 200. Thus, the insert 200 provides a funnel-like, conical insert that has an internal channel, which excludes swabs, wherein a pipette inserted into or through the insert comprises an orifice which is in fluid communication with the contents of the container. The insert 200 is also configured to receive a pipette (e.g, 1000 mΐ tip), which can be positioned at varying depths within the insert, to add and/or remove liquid within the container 100 without obstruction. The insert 200 can be formed from a variety of (transparent, translucent or opaque) materials (e.g, glass, plastic, polymer, metal, etc.) that exhibit the desired strength and chemical properties (e.g. inert) as suited for the particular sample to be housed therein. In some embodiments, the insert 200 is formed as a unitary component where all structural features (e.g. sidewall(s), rim, etc.) are integrally formed. Alternatively, in some embodiments the insert can be formed from a plurality of discrete components that are joined (e.g. mechanically via interlocking features, welding, and/or adhesively) together to form the insert.

[0054] In accordance with an aspect of the disclosure, the insert can be formed with a variety of geometries. In the exemplary embodiments shown in Figs. 4A and 5B, the insert 200 has a length that is approximately equal to the container 100 length A (where length A is the internal depth of the container). In this embodiment, the insert can be formed as a plurality of components including an upper section 201 having a rim and frustroconical section 202, which connects to a lower section 203. Lower section 203 can include a closed distal end 205, and a plurality of apertures 204 (of uniform or varying size and/or distribution around the insert); at least one of the apertures 204 establishing fluid communication between the internal channel of the insert and the contents of the container (which are external to the insert). The upper 202 and lower 203 sections can be provided in a variety of lengths and tapers, with the interfacing diameters of these two sections remaining common, such that an insert of any desired length can be readily assembled by selecting the desire lengths and connecting the upper and lower sections together.

[0055] In the exemplary embodiment shown in Fig. 4B, the insert 200 has a length that is less than the container 100 length A, such that the insert does not contact the bottom of the container 100 when inserted therein. In some of the embodiments, the insert 200 has a length which is sufficient to displace a carrier(s) within the container, such that the internal channel of the insert is free of carriers. The insert can include apertures 214 that are elongate in shape, and disposed at alternating heights along the container sidewall 220, as shown. Optionally, the insert can also include an aperture/opening at the distal end of the insert. [0056] In the exemplary embodiments shown in Figs. 4C and 5A, the insert 200 has a length that is less than the container 100 length A, such that the insert does not contact the bottom of the container 100 when inserted therein. As shown, the insert includes an aperture/opening 224 at the distal end of the insert, while the sidewall 220 of the insert is a contiguous surface (does not include apertures). Also, in some embodiments the insert 200 further includes a pierceable upper surface 230 (e.g., a foil seal or membrane) that covers the proximal end of the insert 200, above the internal channel, as shown in Fig. 4C. This cover 230 can serve as a tamper-evident closure to the insert, alerting a user if the device has been damaged or previously used, and thus at risk of contamination in subsequent uses.

[0057] In the exemplary embodiments shown in Fig. 4D-E, the insert 200 can include a ring that sealingly engages the mouth of the container and forms a downwardly projecting skirt that couples the insert to the container. The skirt can increase the surface area of the insert that contacts the container to increase frictional forces and provide a more secure union between the insert and container (e.g. sufficient to withstand handling, shaking procedures, transport, etc.). As shown, the skirt can be formed from a first sidewall 211 at the proximal end of the insert, and having a diameter sized to matingly receive the mouth of the container. For example, the sidewall 211 can be sized to engage an interior surface of the container 100, and/or an exterior surface of the container 100, as desired. The respective diameters can be sized for snap (or “interference”) fit assembly. In some embodiments, the proximal end of the sample container is coupled to the insert device via press-fit, pressure-fit, friction-fit, snap-fit, or twist-to-fit connection or via one or more fasteners. As shown in Fig. 4D, the sidewall 211 can extend downwardly a distance “D”. In some embodiments, this sidewall 211 extends a depth “D” such that the bottom edge of the sidewall is located below (or distal) to the proximal ends of the swabs housed within the container 100; this prevents the swab shafts from entering the central internal channel of the insert 200. A second sidewall 220 forms the internal channel, which remains free of swabs, for receiving the pipette 400 at its open proximal end, and establishing fluid communication between an orifice of the pipette and the fluid within the container 100.

[0058] Additionally or alternatively, the skirt can be sized to be positioned entirely within the container 100, at a depth spaced from the mouth of the container. For example,

Fig. 4F depicts an exemplary insert 200 having a skirt formed from a sidewall 211 that is received within and abuts the interior surface of the container.

[0059] In the exemplary embodiments shown in Fig. 4F, the insert 200 can include a ring having a multiple sidewalls 211 and 212 at the proximal end of the insert to matingly receive the mouth of the container. For example, the sidewall 211 can be sized to engage an interior surface of the container 100, while sidewall 212 engages an exterior surface of the container 100, such that the rim of the container is sandwiched between the two downwardly extending sidewalls 211 and 212 of the insert ring. In the exemplary embodiment shown, sidewall 211 extends to a depth “D” that is greater than the depth “d” of sidewall 212. Accordingly, this greater depth of the internal sidewall allows a visual confirmation (from a vantage point external of the container and insert) that the insert has been properly inserted ( e.g insert 200 is concentric to the container 100), and has established a secure seal ( e.g ., a sidewall is visible on both sides, or “sandwiching”, the container). Similarly to the prior description of embodiment in Fig. 4E, the respective diameters of sidewalls 211 and 212 can be sized for threaded or snap (or “interference”) fit assembly onto the container. Likewise, sidewall 220 forms the internal channel, which remains free of swabs, for receiving the pipette 400 at its open proximal end, and establishing fluid communication between an orifice on the pipette and the fluid within the container 100. In some embodiments, the internal channel of the insert is free of the carriers/swabs when there are no carriers/swabs present within the channel, such that the channel is empty with its internal volume fully available for fluid transfer.

[0060] According to another aspect of the disclosure, the sidewall(s) of the insert 200 engage the container to self-orient the insert with respect to the container. For example, as the sidewall(s), 211 and/or 212, of the insert 200 engage the mouth of the container 100, the longitudinal axis of the insert (which runs through the center of the internal channel) is aligned with the central longitudinal axis of the container 100. This brings the insert into concentric alignment with the container, while the sidewall of the internal channel simultaneously displacing any swabs such that the internal channel is both: free of any swabs, and positioned in the middle of the container opening so that the pipette can be readily inserted without risk of obstruction.

[0061] In some embodiments, the container 100 includes threads on the exterior surface of its sidewalls at the proximate end, and the insert includes complimentary threads on the interior surface of sidewall 211 in Figures 4D or Figure 4E, or on the interior surface of sidewall 212 in Figure 4F. This allows for the insert 200 to be threadably coupled to the container 100 so that the insert can be readily removed and replaced, as desired. In some embodiments, the container 100 is configured to be snap-fit to the insert, e.g., the container 100 has a portion on its proximal end which snap-fits into a portion of sidewall 211 in Figures 4D or Figure 4E, or into a portion of sidewall 211 or sidewall 212 of Figure 4F.

[0062] Figures 6A-C depict additional views of the exemplary embodiment of the present disclosure in which the insert 200 includes a ring. Fig. 7 depicts a cross-sectional view taken along reference plane A-A as shown in Fig. 6A.

[0063] In some embodiments, a cap can be included for sealing the opening, at the proximal end, of the internal channel of the insert. In the exemplary embodiment shown in Fig. 8, the cap 300 can have an undulating lip 310 circumscribing the cap. This undulating lip provides an ergonomic grip for a user to grasp the cap and remove it from the insert 200.

In some embodiments, the cap 300 can include a downwardly projecting plug 320, the plug 320 sized with a diameter that facilitates occlusion via interference fit within the internal channel of the insert 200 when the cap is inserted thereon to prevent leakage. Additionally or alternatively, the cap 300 can include a threaded connection to the insert 200. Additionally or alternatively, the cap 300 can be configured to be snap-fit, press-fit, pressure-fit, friction-fit, or twist-to-fit or connected via one or more fasteners to the insert 200. Additionally or alternatively, the cap 300 can be tethered to the insert 200 via a flexible connector. For example, the bulbous portion 310 of the cap can have internal threads that engage complimentary threads on the outer circumference of the insert 200.

[0064] In accordance with another aspect of the disclosure, a method of using the device includes providing a container 100 having a central longitudinal axis and housing a plurality of carriers (e.g., swabs). The swabs can be housed within the container in any disorganized or jumbled manner. The insert 200 is placed within the container with the sidewall(s) defining the ring engaging the container to concentrically align the insert 200 and container 100. Additionally, the sidewall defining the internal channel of the insert displaces the swabs 10 radially outward and/or circumferentially around the insert such that the internal channel remains free and clear of any swabs 10. The internal channel of the insert can be sized with a (tapered) diameter configured to occupy enough volume of the container that forces the swabs to be distributed around the perimeter of the internal channel. Next, the pipette 400 can then be positioned within the (unobstructed) internal channel of the insert, as shown in Fig. 9, and fluid addition/removal through the internal channel of the insert can then be performed

[0065] In some embodiments the pipette 400 is displaced the entire depth of the container such that the pipette orifice is positioned at the bottom of the container, and this can be done with the pipette 400 sill housed within the insert 200 (as is the case with the insert embodiments shown in Fig. 4A), or the pipette can extend beyond the internal channel of the insert such that the pipette orifice is spaced from the distal end of the insert (as is the case with insert embodiments shown in Fig. 4C-F; and 9). Thus, the pipette does not directly engage or contact the swabs 10, and the pipette orifice is free of any interference or interruption of fluid transfer. Also, as shown in the exemplary embodiment of Fig. 11, the pipette can have a diameter smaller than the diameter of the internal channel such that the pipette also does not directly engage or contact the insert 200. Furthermore, the pipette orifice is spaced from the openings 204 of the insert 200. In some embodiments, a first object (e.g. pipette) remains spaced from a second object (e.g. swab(s)) so that the first object does not touch the second object. Additionally or alternatively, the first object (e.g. pipette) can remain spaced from a known location reference point, such as the distal end of the insert. [0066] In accordance with another aspect of the disclosure, an exemplary operation of the device disclosed herein includes receiving a container 100 (e.g. concentric tube) that includes a plurality of swabs (at least one swab including a biological sample) with the bulbous end dispose downwardly at located at the closed distal end of the container 100. The container 100 can be dry, or include a fluid already disposed therein (with a sealing cap to prevent premature leakage during transit and handling). The cap of the container can be removed (if present), and a fluid, e.g. a liquid or buffer such as water, a saline solution or phosphate buffered saline (PBS), for example 6 mL of PBS, can be dispensed within the container to at least partially submerge the samples carried by the swabs. The cap can then be repositioned on the container, with the contents of the container then being subject to mixing, shaking or a vortex, e.g., for a predetermined time, e.g. 30 seconds. Thereafter, the contents of the container can be incubated for a predetermined time period, e.g. 10 minutes and at a predetermined temperature, e.g. room temperature. The identifying label, e.g. a QR code or a barcode, if any, on the container is mapped to a corresponding sample container. Once synced, the container 100 (e.g. a Falcon tube or Micronic™ tube) is uncapped, the insert device disclosed herein can be inserted into the container (thereby displacing the swabs to prevent interference with the pipette) and a predetermined amount, e.g. 800 pL, of solution is removed from the container 100 via the pipette 400 inserted within the internal channel of the insert and dispensed into a second container. In some embodiments a plurality of containers can be accessed in a bulk processing step, e.g. 88 tubes can be assembled on a rack for simultaneous fluid handling. After the fluid transfer to the second container(s), the second contained s) can be recapped, with the initial container(s) 100 discarded.

[0067] For purpose of illustration and not limitation, an exemplary embodiment of the present disclosure can include a plurality (e.g, twenty-five) of swabs, of a uniform type (e.g, dimensions) or a variety (e.g, three distinct types) of different swab types, housed within a single container.

[0068] In some embodiments, at least one of the steps of placing an insert, placing a pipette, or removing or adding fluid is performed by a machine or robot and/or is a step in an automated or partially automated process.

[0069] In some embodiments, fluid disposed within the sample container is removed through the pipette, and wherein, in one or more additional steps, the removed fluid is analyzed, directly or indirectly, for the presence or absence of a nucleic acid molecule of a disease-causing agent.

[0070] In some embodiments, the disease-causing agent is SARS-CoV-2, and the nucleic acid molecule encodes a spike or a nucleocapsid protein or a portion thereof, and wherein the disease-causing agent is SARS-CoV-2.

[0071] Dosing Cap

[0072] In accordance with another aspect of the disclosure, a fluid handling device can include a removable cap sized to engage the container and transfer a volume (e.g., collect a predetermined dosage) of fluid. In some embodiments, the device for handling liquids includes: a cap for a sample container, wherein the sample container comprises an open proximal end and a closed distal end, and the cap is capable of sealing the open proximal end of the sample container, and the cap comprises a movable internal chamber, the movable chamber comprising at least two orifices (e.g., at least one air hole and at least one fluid inlet/outlet hole). In some embodiments, when a fluid (e.g., comprising a diluent and one or more samples) is dispensed into the sample container (e.g., through an open proximal end of the sample container), the sample container can be sealed with a cap comprising a movable internal chamber, wherein the movable chamber comprises at least two orifices; the sample container can then be inverted, such that the fluid drains into the movable internal chamber via a first orifice (e.g., a fluid inlet/outlet hole), and air can escape from the movable internal chamber via a second orifice (e.g., an air hole); and the movable inner chamber can then be moved, allowing the fluid to flow out of the internal chamber, where it can then be further processed (e.g., collected into a second sample container, analyzed for the presence of an analyte, studied, stored, etc.).

[0073] In some embodiments, the cap be threaded or snapped (e.g., snap-fitted) onto the open proximal end of the sample container. In some embodiments, the cap (whether open or closed) can be attached to the sample container via a tether or flexible connector. In some embodiments, a diluent is a buffer, water, or a saline solution. In some embodiments, a diluent is phosphate buffered saline (PBS).

[0074] In some embodiments, the present disclosure pertains to: a method of handling liquids, comprising the steps of:

(A) providing a sample container, comprising an open proximal end and a closed distal end;

(B) providing one or more samples, wherein the one or more samples are optionally carried by one or more carriers;

(C) providing a fluid (e.g., a diluent);

(D) introducing the one or more samples and the fluid into the sample container through the proximal open end, such that the samples and fluid collect at the distal closed end of the sample container;

(E) sealing the proximal end of the sample container with a cap comprising a movable internal chamber, wherein the movable internal chamber comprises an airhole and a fluid inlet/outlet hole;

(F) inverting the sample container such that the samples and fluid collect at the proximal end of the container, and travel through the fluid inlet/outlet hole into the internal chamber, and air is allowed to escape from the internal chamber via the airhole;

(G) moving the movable chamber such that the samples and fluid can flow out of the sample container via the fluid inlet/outlet hole and can be collected for further processing (e.g., collected into a second sample container, analyzed for the presence of an analyte, studied, stored, etc.). [0075] In some embodiments, the shape and size of the cap and the movable inner chamber are configured so that they do not come into physical contact with carriers, if any, wherein the carriers carry the samples inside the sample container.

[0076] In some embodiments, the cap is attached with threads, snaps on, or is attached to the sample container via a tether or flexible connector.

[0077] In the exemplary embodiment shown in Figs. 13A-D, a diluent and sample

(biological, chemical, etc.) can be dispensed into the container 1000 via the container’s proximal end, or “mouth”, as shown in Fig. 13A. A removable cap 3000 is then placed on the proximal end to sealingly engage the sidewalls of the container 1000, as shown in Fig. 13B. The cap can included a threaded coupling with the container, and have a sealing ring comprising multiple sidewalls, as described above with reference to the embodiment of Figs. 4-9. Additionally, the cap 3000 can be formed from a plurality of discrete components, including a plunger 3002, a lid 3006, and an internal chamber 3004. The plunger 3002 and chamber 3006 include complementary walls with coinciding orifices 3010 and 3012. In the exemplary embodiment shown, the orifices are at different or offset heights, with the first (liquid) orifice 3012 located closer to the mouth of the container, and the second (air vent) orifice 3010 located closer to the chamber 3004 endwall.

[0078] The plunger 3002 and chamber 3004 can move in tandem (e.g. translate upwardly/downwardly) relative to the lid 3006. As shown in Fig. 13B, the plunger 3002 an chamber 3004 are positioned within the interior of the container with the fluid contents of the container (e.g. diluent + sample) disposed, via gravitational force or centrifugation, at the bottom of the container while the chamber 3004 is empty (i.e. contains only air).

[0079] When the container and cap assembly is inverted, as shown in Fig. 13C, the liquid contents of the container (diluent + sample) are drawn, via gravitational force or centrifugation, downwardly towards the (inverted) mouth of the container. The liquid contents (diluent + sample) pass through the orifice 3012 to enter the chamber 3004 of the cap, while simultaneously forcing the air to exit the chamber via orifice 3010 and ascend upwardly towards the (inverted) bottom of the container. In some embodiments, the chamber 3004 can be sized according to a dosage regimen (e.g. 800 mΐ) such that a full chamber 3004 corresponds to a predetermined amount of liquid, with any excess liquid remaining sealed within the container and unable to exit unless the lid 3006 is removed.

[0080] As shown in Fig. 13D, a user can then grab the plunger 3002 and move the plunger so as to bring the chamber 3004 outside of the container 1000. Once the orifices 3010 and 3012 are moved into their extended position outside of the container, the liquid contents (diluent + sample) can be accessed for further processing, e.g. drained into a second sample container, studied, stored, analyzed for the presence of an analyte or other compound of interest, etc. In some embodiments the proximal and distal ends of the plunger 3002 and chamber 3004 include laterally extending flanges which serve as a motion limiter, or “stop”, to limit the range of motion of the plunger/chamber combination.

[0081] Accordingly, this embodiment provides a custom cap with a two-phase toggle for use after the diluent is added and incubated to allow for material diffusion off the swabs. Once this phase is finished, the tube is flipped upside down, and the dosing chamber is flooded (allowing air to escape through the top hole). After flooding, the cap is toggled open, and dosed fluid is allowed to escape (again, using the same air hole to allow the fluid to escape.

[0082] Puncture Tube

[0083] In accordance with another aspect of the disclosure, a fluid handling device can include the sample container body itself configured to perform as a swab exclusion device. For example, a hole can be made (via sharp puncture, laser, etc.) on the distal end of the sample container, potentially while it is inverted (e.g., such that the fluid comprising a sample is on the opposite end than the end in which the hole is made. Then the tube is reoriented above a second container (e.g., a destination container), and air is permitted into the sample container to allow a certain volume of liquid to escape. In some embodiments, an airhole is also made in the sample container to facilitate fluid moving from the sample container to the second container.

[0084] In some embodiments, the system comprises a device capable of creating a hole in or near the closed distal end of a first sample container, and a second container capable of capturing fluid and sample which flows from the created hole in the first sample container. In some embodiments, the hole is produced by puncturing, drilling, ablation (e.g., ablation via a laser), or slicing or cutting (e.g., slicing or cutting off part of the distal end of the container, for example, using a laser or a blade).

[0085] Additionally or alternatively, a method of handling liquid is disclosed comprising the steps of:

(A) providing a first sample container, comprising an open proximal end and a closed distal end;

(B) providing one or more samples, wherein the one or more samples are optionally carried by one or more carriers; (C) providing a fluid (e.g., a diluent);

(D) introducing the one or more samples and the fluid into the first sample container through the proximal open end, such that the samples and fluid collect at the distal closed end of the first sample container;

(E) creating a hole in or near the distal closed end of the sample container;

(F) allowing the samples and fluid to flow from the first sample container through the created hole; and

(G) collecting at least a portion of the fluid in a second sample container for further processing (e.g., collected into a second sample container, analyzed for the presence of an analyte, studied, stored, etc.).

[0086] Additionally or alternatively, a method of handling liquid is disclosed comprising the steps of:

(C) providing a fluid (e.g., a diluent);

(E) closing or sealing the first sample container, and inverting the first sample container such that the fluid collects at the proximal end of the first sample container;

(F) creating an outlet hole in or near the distal closed end of the first sample container;

(G) re-orienting the first sample container such that the fluid collects at the distal end of the first sample container;

(H) optionally creating an airhole in the first sample container, wherein this step can be performed before or after any of steps (A) to (G);

(I) allowing the fluid to flow from the first sample container through the outlet hole in or near the distal end of the container; and

(J) collecting at least a portion of the fluid in a second sample container for further processing (e.g., such that the fluid can be analyzed for the presence of an analyte, studied, stored, etc.).

[0087] In the exemplary embodiment shown in Fig. 14, a container 1100 is provided for receiving a biological sample and solution, as described above. A removable cap 3100 is also included for sealingly engaging the container (e.g. via threaded coupling as described in reference to the embodiments of Fig. 8 above, or via a snap-fit coupling). A piercing member 5000 creates an opening or hole within the closed distal end of the container to form an egress point to allow the fluid contents to escape the container 1100.

[0088] In some embodiments the frangible portion of the container that is ruptured to create the opening is displaced upwardly into the interior of the container 1100. In some embodiment the frangible portion is displaced outwardly or downwardly, e.g. to create a flat that rotates away from the interior of the container. In some embodiments, the frangible portion is retained by the piercing element itself 500.

[0089] The piercing member 5000 can be symmetric so as to create uniform opening in the container. Although the exemplary embodiment shows a single piercing member creating a single opening, a plurality of piercing members can be employed to create a plurality of openings in the container. Also, the piercing member 5000 can include an external shroud surrounding the perimeter of the piercing member 5000 that forms a fluid tight seal against the exterior surface of the container 1100 to prevent any undesired leaking of the fluid upon creation of the hole. Although this illustrated embodiment depicts a mechanical piercing tool 5000, additional or alternative apparatus can be used to create the opening, e.g. laser.

[0090] Additional Exemplary Embodiments

[0091] In some embodiments, the device can be used in a process related to pool testing, which involves simultaneous testing of multiple samples, wherein two or more of the samples are from different individuals or sources.

[0092] In some embodiments, the device can be used for liquid handling in sample containers containing a collection of samples (e.g., multiple carriers, each carrying a sample from an individual or a single source). In some embodiments, at least two of the samples can be from different individuals or sources, and/or at least two of the samples can be from the same individual or source.

[0093] In some embodiments, the sample is a pool sample (or pooled sample) collected from a plurality of individuals or sources (e.g., at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,

12, 13,14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, or more individuals or sources). In some embodiments, a source is a location in the environment, and the sample is tested for a pollutant or contaminant or other hazardous compound or chemical or biological agent. In some embodiments, pool testing is effective for economically testing groups of individuals or sources, as the testing of pool samples consumes fewer reagents, less lab time, etc., than testing the corresponding individual samples. In some embodiments, a pool sample comprises samples from individuals ( e.g ., members of the pool) who live and/or work in or near the same location. In some embodiments, a pool sample comprises samples from multiple individuals (e.g., members of the pool), at least some of whom have regular contact with each other. In some embodiments, members of a pool: all live in locations near to each other; are all students or employees of the same educational institution; live in the same or adjacent dorms; work in the same or adjacent workplaces; etc. In some embodiments, pool testing can be used for environmental testing, wherein multiple samples from different locations in an environment are tested (e.g., for a toxin, poison, radioactive material, etc.).

[0094] In some embodiments, a pool sample can be tested for a disease, including but not limited to a communicable disease. In some embodiments, prior to testing a pooled sample, the individual members of the pool are individually tested for the presence of a disease-causing agent (e.g., a virus, bacterium, fungus, cancerous cell, etc.), wherein members who have tested positive are removed from the pool, and only individuals suspected of being or known to be negative are included in the pool. In some embodiments, pool testing is effective for economically testing the same group of individuals repeatedly (e.g, multiple times a week or month). In some embodiments, the disease is related to SARS-CoV-2.

[0095] In some embodiments, a method for detecting a molecule of interest in a pool sample comprises the steps of:

(A) providing two or more individual samples, each sample having been collected from an individual or a source, wherein each sample is carried by a carrier;

(B) combining the two or more carriers carrying the two or more samples in a sample container;

(C) inserting a device into the sample container, wherein the device is a device for handling fluid in a sample container as described herein;

(D) dispensing a fluid into the sample container, wherein the fluid can be in fluid contact with the samples, wherein step (D) can optionally be performed prior to any of steps (A), (B) or (C), or after step (C);

(E) optionally shaking or vortexing the sample container such that the fluid is mixed with the samples; and/or optionally centrifuging the sample container;

(F) withdrawing, via a pipette inserted into the container and through the device, the one or more fluids, such that the fluid can be further processed to determine the presence or absence of the molecule of interest. [0096] In some embodiments, the fluid is or comprises a buffer and/or a preservative capable of preserving the sample.

[0097] In some embodiments, the molecule of interest is: a toxin, poison, radioactive material, etc. etc. In some embodiments, a molecule of interest is: a nucleic acid molecule, protein, or other component of a disease-causing agent. In some embodiments, a disease- causing agent is a virus or bacterium. In some embodiments, the disease-causing agent is SARS-CoV-2. In some embodiments, the nucleic acid encodes the spike (S) protein or the nucleocapsid (N) protein of SARS-CoV-2.

[0098] In some embodiments, one or more steps in the method is performed by an automated device or in an automated method.

[0099] In some embodiments, a method for detecting a molecule of interest in a pool sample comprises the steps of:

(A) providing a sample container containing a fluid;

(B) providing two or more samples, wherein at least two of the samples are from different individuals, and wherein each sample is carried by a carrier;

(C) combining two or more carriers carrying two or more samples in the sample container;

(D) optionally shaking or vortexing the sample container to increase the mixing of the fluid and the samples, such that after step (C) and/or optional step (D), the fluid comprises the samples; and/or optionally centrifuging the sample container;

(E) inserting a device into the sample container, wherein the device is a device for handling fluid in a sample container as described herein, wherein steps (D) and (E) or the sub-steps thereof can be performed in any order; and

(F) removing, via a pipette inserted into the container and through the device, at least a portion of the fluid comprising the samples, such that the one or more fluids can be further processed to determine the presence or absence of the molecule of interest.

[00100] In some embodiments, a method for detecting a molecule of interest in a pool sample comprises the steps of:

(A) providing two or more samples, wherein each sample is from an individual or a source, wherein each sample is carried by a carrier;

(B) combining two or more carriers in a sample container;

(C) inserting a device into the sample container, wherein the device is a device for handling fluid in a sample container as described herein; (D) dispensing a fluid into the sample container, and optionally vortexing or shaking the sample container, such that the fluid comprises the samples;

(E) withdrawing the fluid, via a pipette inserted into the container and through the device, such that the fluid comprising the samples can be further processed to determine the presence or absence of the molecule of interest.

[00101] In some embodiments, a method for detecting a nucleic acid molecule of a disease-causing agent in a pool sample comprises the steps of:

(B) combining two or more carriers in a sample container;

(D) dispensing a fluid into the sample container, and optionally vortexing or shaking the sample container, such that the fluid comprises the samples;

(E) withdrawing the fluid, via a pipette inserted into the container and through the device, such that the fluid comprising the samples can be further processed to determine the presence or absence of the nucleic acid molecule of the disease-causing agent.

In some embodiments, the disease-causing agent is SARS-CoV-2. In some embodiments, the nucleic acid encodes the spike (S) protein or the nucleocapsid (N) protein of SARS-CoV-2.

[00102] In some embodiments, a method for detecting a nucleic acid molecule of a disease-causing agent in a pool sample comprises the steps of: providing samples from two or more individuals (e.g., wherein the number of individuals is equal to, less than or greater than the number of samples), wherein each sample is carried by a carrier (e.g., a swab); combining two or more carriers and a fluid to create a pool sample (e.g., a pooled sample) in a sample container; inserting the device into the sample container, wherein the device is a device for handling fluid in a sample container as described herein; inserting a pipette (e.g., by hand or using an automated machine, robot or system) into or through the device such that an orifice in the pipette is in fluid communication with the pool sample; using the orifice in the pipette to remove at least a portion of the pool sample; extracting nucleic acids from the pool sample; amplifying the nucleic acids, using primers which are complementary to a nucleic acid sequence related to a disease-causing agent or a control, wherein the primers optionally each comprise a unique barcode (index); optionally, cleaning up the pool samples; combining products of the amplification of the nucleic acids in the pool sample; sequencing the products; deconvoluting the results using the barcodes (indexes), if any, to correlate results with the pool samples; and communicating the results, directly or indirectly, to one or more of the individuals. In some embodiments, the detection of an amplification product of a nucleic acid associated with a disease-causing agent is indicative of at least one individual who provided a sample being positive for the presence of the disease-causing agent. In some embodiments, the disease-causing agent is a virus, bacterium, fungus or cancerous cell. In some embodiments, the disease-causing agent is SARS-CoV-2. In some embodiments, the disease-causing agent is SARS-CoV-2 and the nucleic acid sequence is a portion of the coding segment for a SARS-CoV-2 spike protein or nucleocapsid protein. In some embodiments, testing of pooled samples is particularly efficacious if the incidence or suspected incidence of SARS-CoV-2 is low.

[00103] While the disclosed subject matter is described herein in terms of certain preferred embodiments, those skilled in the art will recognize that various modifications and improvements may be made to the disclosed subject matter without departing from the scope thereof. Moreover, although individual features of one embodiment of the disclosed subject matter may be discussed herein or shown in the drawings of the one embodiment and not in other embodiments, it should be apparent that individual features of one embodiment may be combined with one or more features of another embodiment or features from a plurality of embodiments.

[00104] It will be apparent to those skilled in the art that various modifications and variations can be made in the method and system of the disclosed subject matter without departing from the spirit or scope of the disclosed subject matter. Thus, it is intended that the disclosed subject matter include modifications and variations that are within the scope of the appended claims and their equivalents.

Claims

1. A device for handling fluid in a sample container, the sample container having an open proximal end and a closed distal end and being configured to receive a fluid and at least one carrier carrying a sample, wherein the fluid can be in fluid communication with the sample, the device comprising: an insert having a proximal end and a distal end, the insert being configured to be coupled to the sample container and having: a first sidewall defining a first diameter at the proximal end, a second sidewall defining a second diameter at the proximal end, and a third sidewall defining an internal channel which is open at the proximal end and has at least one opening at or near the distal end, such that when the device is inserted into the sample container, the first and/or second sidewall contact the proximal end of the sample container, and wherein: the internal channel is configured to receive a pipette comprising an orifice, wherein the orifice can be in fluid communication with the fluid within the sample container.

2. The device of claim 1, wherein, when the device is inserted into the sample container, the internal channel of the insert is free of the carrier(s).

3. The device of claim 1, wherein the at least one carrier is a swab.

4. The device of claim 1, wherein the third sidewall of the insert is frustoconical.

5. The device of claim 1, wherein the proximal end of the sample container is coupled to the device via a threaded, press-fit, pressure-fit, friction-fit, snap-fit, or twist-to-fit connection or via one or more fasteners.

6. The device of claim 1, further comprising a cap, the cap being configured to seal the opening in the proximal end of the insert.

7. The device of claim 6, wherein the cap is removably coupled to the insert via a threaded, press-fit, pressure-fit, friction-fit, snap-fit or twist-to-fit connection or via one or more fasteners, and/or the cap is tethered to the insert via a flexible connector.

8. The device of claim 1, wherein the insert further comprises a pierceable upper surface sealing the open proximal end of the inner channel of the insert.

9. The device of claim 1, wherein at least one of the first sidewall or second sidewall of the insert engages the proximal end of the sample container to concentrically align the insert with the sample container.

10. A device for handling fluid in a sample container, wherein the sample container has an open proximal end and a closed distal end, the sample container being configured to receive a fluid and at least one carrier carrying a sample, wherein the fluid can be in fluid communication with the sample, the device comprising: an insert, the insert being capable of being coupled to the proximal end of the sample container and having: a first diameter at a proximal end, a second diameter at a distal end, and a sidewall defining an internal channel, wherein the internal channel has an open proximal end and is in fluid communication with the fluid within the sample container via at least one hole in the sidewall; wherein placement of the insert within the sample container displaces the carrier(s) so that the internal channel is free of the carrier(s).

11. The device of claim 10, wherein the insert has a tapered sidewall.

12. The device of claim 10, wherein the proximal end of the insert includes a sealing ring, the sealing ring configured to engage the proximal end of the sample container.

13. The device of claim 12, wherein the sealing ring engages an interior surface and an exterior surface of the sample container.

14. The device of claim 12, wherein the sealing ring concentrically aligns the insert with the sample container.

15. The device of claim 10, wherein the at least one carrier is a swab.

16. The device of claim 10, wherein the insert further comprises a pierceable upper surface sealing the open proximal end of the inner channel of the insert.

17. The device of claim 10, wherein the proximal end of the sample container is coupled to the device via a threaded, press-fit, pressure-fit, friction-fit, snap-fit, or twist-to-fit connection or via one or more fasteners.

18. The device of claim 10, further comprising a cap, the cap configured to releasably seal the opening in the proximal end of the device via a threaded, press-fit, pressure-fit, friction- fit, snap-fit or twist-to-fit connection or via one or more fasteners, and/or the cap is tethered to the insert via a flexible connector.

19. A method of handling fluid in a sample container comprising: providing a sample container including a fluid and at least one swab carrying a sample, wherein the fluid is in fluid communication with the sample; placing an insert within the sample container, the insert having: a first diameter at a proximal end, a second diameter at a distal end, and a sidewall defining an internal channel; wherein placement of the insert within the sample container displaces the swab(s) within the sample container such that the internal channel is free of the swab(s); placing a pipette at least partially within or through the internal channel of the insert, such that an orifice on the distal end of the pipette is in fluid communication with the fluid; and removing and/or adding fluid disposed within the sample container through the pipette.

20. The method of claim 19, wherein placing the insert within the sample container includes engaging an interior surface of the sample container and an exterior surface of the sample container with a portion of the insert.

21. The method of claim 19, wherein the pipette remains spaced from the swab(s) during fluid removal.

22. The method of claim 19, wherein the sample container has a central longitudinal axis and the internal channel of the insert is aligned with the central longitudinal axis.

23. The method of claim 19, wherein displacement of the swab(s) includes distributing the swabs evenly around the central longitudinal axis of the sample container.

24. The method of claim 19, wherein the orifice at a distal end thereof, the pipette orifice disposed at a location spaced from the distal end of the insert.

25. The method of claim 19, wherein the pipette orifice is disposed at a location spaced from at least one opening in the insert sidewall.

26. The method of claim 19, further comprising dispensing fluid from the pipette into the sample container.

27. The method of claim 19, wherein removing fluid includes automatically positioning at least one pipette above the sample container.

28. The method of claim 27, wherein automatically positioning at least one pipette above the sample container includes positioning a plurality of pipettes above a plurality of sample containers with a robotic armature.

29. The method of claim 27, wherein the at least one pipette is automatically displaced downward a predetermined depth into the sample container.

30. The method of claim 19, wherein at least one of the steps of placing an insert, placing a pipette, or removing or adding fluid is performed by a machine or robot and/or is a step in an automated or partially automated process.

31. The method of claim 19, wherein fluid disposed within the sample container is removed through the pipette, and wherein, in one or more additional steps, the removed fluid is analyzed, directly or indirectly, for the presence or absence of a nucleic acid molecule of a disease-causing agent.

32. The method of claim 31, wherein the disease-causing agent is SARS-CoV-2.

33. The method of claim 31, wherein the nucleic acid molecule encodes a spike or a nucleocapsid protein or a portion thereof, and wherein the disease-causing agent is SARS- CoV-2.

34. A method of handling fluid in a sample container comprising: providing a sample container including a fluid and at least one swab carrying a sample, wherein the fluid is in fluid communication with the sample; placing the device of claim 1 or the device of claim 10 within the sample container, placing a pipette at least partially within or through the internal channel of the insert of the device, such that an orifice on the distal end of the pipette is in fluid communication with the fluid; and adding fluid and/or removing fluid which is in fluid communication with the sample from the sample container through the pipette.

35. The method of claim 34, wherein the method comprises the step of removing fluid which is in fluid communication with the sample from the sample container through the pipette.

36. The method of claim 35, wherein, in one or more additional steps, the removed fluid is analyzed, directly or indirectly, for the presence or absence of a nucleic acid molecule of a disease-causing agent.

37. The method of claim 36, wherein the disease-causing agent is SARS-CoV-2.

38. The method of claim 36, wherein the nucleic acid molecule encodes a spike or a nucleocapsid protein or a portion thereof, and wherein the disease-causing agent is SARS- CoV-2.