Oral fluid collector analysis aids, oral fluid collection assembly systems, and methods for extracting representative oral fluid samples from oral fluid collection assemblies

Abstract

An oral fluid collector analysis aid is disclosed, including an isolation platform having lateral dimensions sized to be disposed within a lumen of a sample tube of an oral fluid collection assembly, the isolation platform including a superior surface arranged to contact an oral fluid collection absorbent substrate of the oral fluid collection assembly and an inferior surface distal across the isolation platform from the superior surface. An oral fluid collection assembly system is disclosed including the oral fluid collector analysis aid and the oral fluid collection assembly. A method for extracting a representative oral fluid sample is disclosed, including receiving an oral fluid solution in an oral fluid collection assembly, inserting the oral fluid collector analysis aid such that an oral fluid collection absorbent substrate is isolated from the oral fluid solution, and then extracting the representative oral fluid sample from the oral fluid solution.

Description

Atorney Docket No.: 23619-0092-PCTORAL FLUID COLLECTOR ANALYSIS AIDS, ORAL FLUID COLLECTION ASSEMBLY SYSTEMS, AND METHODS FOR EXTRACTING REPRESENTATIVE ORAL FLUID SAMPLES FROM ORAL FLUID COLLECTION ASSEMBLIES RELATED APPLICATIONS

[0001] This application claims the benefit of and priority to U.S. Provisional Patent Application No. 63 / 778,059, filed March 26, 2025, entitled “Oral Fluids Device,” and U.S. Provisional Patent Application No. 63 / 825,113, filed June 17, 2025, entitled “Oral Fluids Device and Methods for Isolating Oral Fluids,” which are hereby incorporated by reference in their entirety.FIELD OF THE INVENTION

[0002] This application is directed to oral fluid collector analysis aids, oral fluid collection assembly systems, and methods for extracting representative oral fluid samples from an oral fluid collection assemblies. More specifically, this application is directed to oral fluid collector analysis aids, oral fluid collection assembly systems, and methods for extracting representative oral fluid samples from an oral fluid collection assemblies that isolate oral fluid collection absorbent substrate from oral fluid solutions.BACKGROUND OF THE INVENTION

[0003] Oral fluid is an important human sample type, or matrix, used to detect the presence of a range of drugs in a human’s system. The importance of these results can be useful in different contexts, including, but not limited to, forensics, employment, or insurance coverage. There are differences between other human sample types. The sample volume needed is much lower with oral fluid. Drug concentrations are present in lower levels in oral fluid than in urine; therefore, lower screening and confirmation levels are required. Oral fluid identifies the parent drug and sometimes the drug metabolite. Urine testing is targeted at the drug’s metabolite. Such sample collection, analysis, and storage are done with the assistance of consumable collection devices such as the Abbott® Quantisal™ Oral Fluid Collection Device, as well as those devices utilized for the same purpose. Devices such as those disclosed in U.S. Patent Application Publication No.Atorney Docket No.: 23619-0092-PCT2006 / 0245977 Al and U.S. Patent No. 10,722,883 B2 are representative of devices commonly employed for oral fluid analysis, and certain of the embodiments disclosed herein may be compatible with oral fluid collection assemblies as disclosed in these publications. In the case of the Abbott® Quantisal™ Oral Fluid Collection Device, the collection device comprises a fluid transport tube, sized to fit into a standard centrifuge tube carriage; a cap to seal the top of the transport tube; a sorbent, sample collection pad attached to the cap via an extended stem holding the sorbent pad; and a buffer solution resting at the bottom of the transport tube. This collection device has dimensions which are suitable for fitting in a centrifuge and accommodating a centrifugation step.

[0004] The process of oral fluid sample collection, analysis, and storage involves two users who are often communicating remotely and may need to maintain a strict chain of custody. The oral fluid collection process begins with the first user, who uses the sorbent pad by placing the pad underneath the sample subject’s tongue until the adequate volume is reached. The volume of sample absorbed by the sorbent will be referred to heretofore as the “first volume.” The collection pad and stem are then placed in the transport tube with the sorbent pad resting inside the buffer solution. The unadulterated buffer solution present in the bottom of an oral fluid collection device will be referred to heretofore as the “second volume.” The complete collection device is then secured in cold storage until the device is ready for shipping to a laboratory. The pad must remain resting in the buffer solution to stabilize the sample and maintain the sample’s integrity. The resulting oral fluid sample in fluidic communication with the buffer solution will be referred to heretofore as the “third volume.” Fluidic communication describes two or more fluids or liquids interspersed within each other.

[0005] Once the collection device reaches the desired laboratory, the device will be held in cold storage until an appropriate laboratory personnel member (the second user) is prepared to prep the device for sample analysis. For sample analysis, the first step is for the second user to extract as much of the first volume from the sorbent pad as possible. After an aliquot of the resulting third volume, the third volume will go on to be analyzed by various analytical chromatographic instrumentation, including but not limited to liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). Currently, lab personnel have two options to maximize the release of the first volume into the second volume.Atorney Docket No.: 23619-0092-PCTThe first technique requires a “squeegee” method whereby the second user must lift the sorbent pad out of the third volume, then the second user must scrape the sorbent pad against the rim and sides of the transport tube until the sorbent pad is dislodged from the stem and returns to the third volume at the bottom of the transport tube. The second user can then aliquot the third volume around the sorbent pad. Scraping the sorbent pad presents challenges to the second user, because it can be a difficult technique and creates more laborious actions in the sample preparation process. Differences in second users’ personal scraping technique can add more variability to third volume recovery, which in turn can negatively affect analysis result accuracy. If the third volume’s recovery rate is low or inconsistent, the results of the analysis may not accurately reflect the type or the concentration of the compounds of interest present. Poor recovery can lead to incorrect calibration and misinterpretation of results. Less than adequate recovery can lead to inconsistent reproducibility, making the techniques between second users across organizations less reliable.

[0006] The alternative technique the second user has is to press a device holding the sorbent pad to the bottom of the transport tube into the third volume and decant the solution into a new vessel. The second user can aliquot from the new vessel containing the third volume.

[0007] There are issues with both techniques to release a full and consistent amount of liquid from the sorbent pad. The techniques result in a partial release of the oral fluid sample contained within the sorbent pad. The partial and inconsistent release of the first volume leads to a data analysis that will not provide results as accurately as possible. In addition to the partial release of the first volume, having the sponge suspended in the third volume ensures some measure of reabsorption which alters the homogeneity of the sample, further impacting third volume recoveries, and potentially decreasing the accuracy of analysis results. Another issue contained with these first volume release methods lies in the sorbent pad resting in the third volume postaliquot. When the second user is done aliquoting the third volume, they will seal the transport tube with the corresponding cap with the sorbent pad resting in the third volume before placing it in cold storage. While the sorbent pad is suspended in the third volume, the sorbent pad will begin to break down in the liquid over an abbreviated period of time. If the second user must aliquot the third volume again, future analysis could then be impacted negatively by any resulting fibers now suspended in the third volume. Should the second user create a workflow for automated sample preparation, the scraping technique produces variable recoveries and is a cumbersome step notAtorney Docket No.: 23619-0092-PCTsuited for automation. The decanting technique also produces variable recoveries, especially as there is no rinsing or other confirmation that the third volume has been adequately transferred to a new vessel. The decanting technique also adds variability to the consumables used, and there is no standard or consistent amount of the third volume that can be captured with this technique, further hindering automation. The sorbent pad degradation can prevent a certain level of success with automation, as there is not necessarily a proven method of aliquoting the sample to avoid the fibers resulting from the breakdown of the sorbent pad. This leaves room to improve the current solution.

[0008] A solution is needed where the second user of the oral fluid collection assembly can consistently extract as much of the first liquid volume from the oral fluid collection sponge as possible without contacting the wetted surfaces of the oral fluid collection assembly. An effective solution for contactless collection sponge isolation — to prevent cross-contamination — should not rely on the variability of a user’s technique or contribute to collection sponge breakdown within samples. There is also a benefit to remaining contactless with any surface that the first, second, and / or third volume(s) contact.

[0009] The weaknesses of using oral fluid collection devices resembling those previously mentioned have informed a series of iterations of devices and a method of using the device to address the aforementioned weaknesses. Attempts to improve upon the device and analysis process sought to aid in obtaining improved third volume recovery, create ease of use for the second user, and reduce the error in oral fluids sample analysis. These solutions should be capable of addressing the oral fluid collection assemblies and oral fluid collection sponge shafts, even if collection sponge shaft geometries may vary. All attempts heretofore have addressed solutions to the oral fluid collection device.BRIEF DESCRIPTION OF THE INVENTION

[0010] In one exemplary embodiment, an oral fluid collector analysis aid includes an isolation platform having lateral dimensions sized to be disposed within a lumen of a sample tube of an oral fluid collection assembly, the isolation platform including a superior surface arranged to contact an oral fluid collection absorbent substrate of the oral fluid collection assembly and an inferior surface distal across the isolation platform from the superior surface.Atorney Docket No.: 23619-0092-PCT

[0011] In another exemplary embodiment, an oral fluid collection assembly system includes an oral fluid collection assembly including a sample tube having a lumen, a cap enclosing a sample tube aperture disposed at a first end of the sample tube, an applicator extending from the cap into the lumen, and an oral fluid collection absorbent substrate extending from the applicator within the lumen, and an oral fluid collector analysis aid including an isolation platfomi having lateral dimensions sized to be disposed within the lumen, the isolation platform including a superior surface facing the sample tube aperture and an inferior surface distal across the isolation platform from the superior surface, wherein when the oral fluid collector analysis aid is disposed within the lumen, the oral fluid collection absorbent substrate contacts the superior surface of the isolation platform and the superior surface of the isolation platfomi is positioned above a maximum oral fluid solution level of the lumen such that an oral fluid solution disposed within the lumen is isolated from the oral fluid collection absorbent substrate.

[0012] In another exemplary embodiment, a method for extracting a representative oral fluid sample from an oral fluid collection assembly includes receiving an oral fluid solution in the oral fluid collection assembly, the oral fluid collection assembly including a sample tube having a lumen, the oral fluid solution being disposed in the lumen, a cap enclosing a sample tube aperture disposed at a first end of the sample tube, an applicator extending from the cap into the lumen, and an oral fluid collection absorbent substrate extending from the applicator within the lumen, removing the cap, the applicator, and the oral fluid collection absorbent substrate from the sample tube, inserting an oral fluid collector analysis aid through the sample tube aperture into the lumen, the oral fluid collector analysis aid including an isolation platform having lateral dimensions sized to be disposed within the lumen, the isolation platform including a superior surface facing the sample tube aperture and an inferior surface distal across the isolation platfomi from the superior surface, reintroducing the cap and the oral fluid collection absorbent substrate to the sample tube such that the oral fluid collection absorbent substrate contacts the superior surface of the isolation platform, collecting the oral fluid solution in a portion of the lumen at a second end of the sample tube such that the oral fluid solution is isolated from the oral fluid collection absorbent substrate, and then extracting the representative oral fluid sample from the oral fluid solution.BRIEF DESCRIPTION OF THE DRAWINGSAtorney Docket No.: 23619-0092-PCT

[0013] FIG. 1 A is a schematic view of a prior art oral fluid collection sub-assembly including a cap, an applicator, and an oral fluid collection absorbent substrate.

[0014] FIG. IB is a schematic view of a prior art oral fluid collection sub-assembly including a sample tube and an oral fluid solution disposed in the sample tube.

[0015] FIG. 1C is a schematic view of a prior art oral fluid collection assembly combining the sub-assemblies of FIGS. 1A and IB.

[0016] FIG. 2A is an oral fluid collector analysis aid, according to an embodiment of the invention.

[0017] FIG. 2B is a schematic view of the oral fluid collector analysis aid of FIG. 2A disposed in an oral fluid collection assembly forming an oral fluid collection assembly system according to an embodiment of the invention.

[0018] FIG. 2C is a schematic view of the oral fluid collector analysis aid of FIG. 2A depicting an analytical fluid transfer device in an oral fluid collection assembly system, according to an embodiment of the invention.

[0019] FIG. 3 A is an oral fluid collector analysis aid with a standoff extending from an inferior surface, according to an embodiment of the invention.

[0020] FIG. 3B is a schematic view of the oral fluid collector analysis aid of FIG. 3A disposed in an oral fluid collection sub-assembly, according to an embodiment of the invention.

[0021] FIG. 3C is a schematic view of the oral fluid collector analysis aid of FIG. 3A disposed in an oral fluid collection assembly forming an oral fluid collection assembly system, according to an embodiment of the invention.

[0022] FIG. 4 is an oral fluid collector analysis aid with a standoff and a retention fitting, according to an embodiment of the invention.

[0023] FIG. 5A is a schematic view of an oral fluid collector analysis aid with a standoff extending from a superior surface, according to an embodiment of the invention.Attorney Docket No.: 23619-0092-PCT

[0024] FIG. 5B is a schematic view of the oral fluid collector analysis aid of FIG. 5 A disposed in an oral fluid collection sub-assembly, according to an embodiment of the invention.

[0025] FIG. 5C is a schematic view of an applicator of a fluid collection assembly being dismounted from a cap and having its oral fluid collection absorbent substrate being removed, according to an embodiment of the invention.

[0026] FIG. 5D is a schematic view of the oral fluid collector analysis aid of FIG. 3 A disposed in an oral fluid collection assembly forming an oral fluid collection assembly system, according to an embodiment of the invention.

[0027] FIG. 6A is an applicator of a fluid collection assembly being inserted into an oral fluid collector analysis aid having a pair of risers with lateral extensions, according to an embodiment of the invention.

[0028] FIG. 6B is the applicator inserted into the oral fluid collector analysis aid of FIG. 6A being rotated such that a superior surface of the applicator is in contact with the lateral extensions, according to an embodiment of the invention.

[0029] FIG. 7A is an oral fluid collector analysis aid with a snap-fit connector, according to an embodiment of the invention.

[0030] FIG. 7B is the oral fluid collector analysis aid with a snap-fit connector of FIG. 7A mounted onto an applicator of a fluid collection assembly, according to an embodiment of the invention.

[0031] Wherever possible, the same reference numbers will be used throughout the drawings to represent the same parts.DETAILED DESCRIPTION OF THE INVENTION

[0032] This description and the accompanying figures, drawings, exhibits, and references provided herein are provided in their entirety. This description and the accompanying figures, drawings, exhibits, and references that illustrate aspects and embodiments of the present invention should not be taken as limiting — the claims define the protected invention. Various mechanical,Atorney Docket No.: 23619-0092-PCTcompositional, structural, electrical, and operational changes may be made without departing from the spirit and scope of this description and the claims. The material of the following accompanying figures, drawings, exhibits, and references may be comprised of metal, polymer, glass, ceramic, or a combination thereof.

[0033] To avoid repetition in the figures and the descriptions below of the various aspects and illustrative embodiments, it should be understood that many features are common to many aspects and embodiments, and may be interchanged and combined between described embodiments under the understanding of one skilled in the art. Omission of an aspect from a description or figure does not imply that the aspect is missing from embodiments that incorporate that aspect. Instead, the aspect may have been omitted for clarity and to avoid prolix description.

[0034] Provided are exemplary embodiments of the present disclosure, in comparison to articles, systems, and methods not utilizing one or more features disclosed herein, that increase analysis efficiency, increase sample accuracy and uniformity, decrease costs, or combinations thereof.

[0035] Referring to FIGS. 1A-C, known oral fluid collection assemblies 10 include a sample tube 12, a cap 14, an applicator 16, and an oral fluid collection absorbent substrate 18. The oral fluid collection absorbent substrate 18 extends from a first end 20 of the applicator 16, and a second end 22 of the applicator 16 is inserted into a retention aperture 24 in the cap 14 to suspend the applicator 16 from the cap 14. The cap 14 is inserted through an aperture 26 at a first end 28 of the sample tube 12 into a lumen 30 within the sample tube 12, sealing the oral fluid collection assembly 10. A second end 32 of the sample tube 12 is configured to receive an oral fluid solution 34, with the oral fluid collection absorbent substrate 18 at least partially suspended in the oral fluid solution 34. The oral fluid collection assembly 10 has a frame of reference in which the cap 14 is considered to be the superior direction and the second end 32 of the sample tube 12 is considered to be the inferior direction. In some embodiments, the lumen 30 includes a superior portion 36 having a larger interior width 38 than an inferior portion 40 of the lumen 30 such that a transition between the superior portion 36 and the inferior portion 40 of the lumen 30 forms a support ledge 42 withinAttorney Docket No.: 23619-0092-PCTthe lumen 30, where the support ledge 42 is superior to a maximum oral fluid solution level 44 of the oral fluid collection assembly 10.

[0036] The oral fluid collection absorbent substrate 18 may be any suitable substrate for collecting oral fluid, including, but not limited to, a sponge, a frit, a pad, or combinations thereof.

[0037] Referring to FIGS. 2A-2C, in one embodiment, an oral fluid collector analysis aid 100 includes an isolation platform 102 having lateral dimensions 104 sized to be disposed within the lumen 30 of the sample tube 12 of the oral fluid collection assembly 10, the isolation platform 102 including a superior surface 106 arranged to contact the oral fluid collection absorbent substrate 18 of the oral fluid collection assembly 10 and an inferior surface 108 distal across the isolation platform 102 from the superior surface 106.

[0038] It will be appreciated that the analysis aid 100 may have any suitable dimensions and that those dimensions may in turn depend on the dimensions of the sample tube 12 and its features with which the analysis aid 100 is intended to interact.

[0039] In some embodiments, the isolation platform 102 has an aspect ratio of diameter to thickness ranging from 2:1 to 10:1, alternatively 3:1 to 7:1, or any sub-range or combination thereof. The isolation platform 102 may have any suitable lateral dimensions 104, including, but not limited to a diameter of 8-12 mm, alternatively 9-11 mm, alternatively 9.5-10.5 mm, alternatively 9.8-10.2 mm, alternatively 9.9-10.1 mm, alternatively 9.95-10.05 mm, alternatively 9.98-10.02 mm, alternatively 10 mm, or any sub-range or combination thereof. The isolation platform 102 may have any suitable vertical dimensions 105, including, but not limited to a height of 1-3 mm, alternatively 1.2-2.8 mm, alternatively 1.5-2.5 mm, alternatively 1.8-2.2 mm, alternatively 1.9-2.1 mm, alternatively 1.95-2.05 mm, alternatively 1.98-2.02 mm, alternatively 2 mm, or any sub-range or combination thereof.

[0040] Where the lumen 30 includes a support ledge 42, the lateral dimensions 104 of the isolation platform may be smaller than the interior width 38 of the superior portion 36 of the lumen 30 and larger than the interior width 38 of the inferior portion 40 of the lumen 30 such that the oralAtorney Docket No.: 23619-0092-PCTfluid collector analysis aid 100 is configured to rest upon the support ledge 42 within the lumen 30 superior to the maximum oral fluid solution level 44 of the oral fluid collection assembly 10.

[0041] The isolation platform 102 may be configured such that fluid located superior to the isolation platform 102 when the isolation platform 102 is disposed within the lumen 30 may pass through the isolation platform 102 or around the isolation platform 102 or both to transfer to the second end 32 of the sample tube 12. The isolation platform 102 may include at least one channel 110 formed from the superior surface 106 of the isolation platform 102 through the isolation platform 102 to the inferior surface 108 of the isolation platform and / or may include at least one channel 110 disposed at a periphery 112 of the isolation platform 102. The platform 102 may have dimensions that leave at least one gap 114 between the sample tube 12 and the isolation platform 102, such as between the edge of the platform 102 and the inner wall of the sample tube 12 and / or when a standoff is used (as discussed subsequently), between the inferior surface 108 of the platform 102 and the support ledge 42.

[0042] The at least one channel 110 may have any suitable channel width 116, including, but not limited to, a channel width 116 sufficient to receive an analyte fluid transfer device 46. The analyte fluid transfer device 46 may be any suitable analyte fluid transfer device 46, including, but not limited to, a capillary tube, a syringe needle, a pipette, or a transfer tube. The superior surface 106 may include sufficient surface area to prevent the oral fluid collection absorbent substrate 18 from passing through or bypassing the isolation platform 102. The at least one channel 110 may have a channel width 116 sufficiently small to prevent the oral fluid collection absorbent substrate 18 from passing through the at least one channel 110. It will be appreciated that the channel width 116 may not be uniform across the at least one channel 110 as seen, for example, in FIG. 2A.

[0043] Referring to FIGS. 3A-C, in a further embodiment, the oral fluid collector analysis aid 100 further includes a standoff 118 extending from the inferior surface 108 of the isolation platform 102, the standoff 118 having a length 120 sufficient to position the superior surface 106 of the isolation platform 102 above a maximum oral fluid solution level 44 of the lumen 30. TheAtorney Docket No.: 23619-0092-PCToral fluid collector analysis aid 100 may include a single standoff 118 or a plurality of standoffs 118.

[0044] The standoff 118 may have any suitable length 120, including, but not limited to a length 120 of 50-70 mm, alternatively 55-65 mm, alternatively 58-62 mm, alternatively 59-61 mm, alternatively 59.5-60.5 mm, alternatively 59.8-60.2 mm, alternatively 59.9-60.01 mm, alternatively 60 mm, or any sub-range or combination thereof.

[0045] The standoff 118 may have any suitable thickness 121, including, but not limited to a thickness 121 of 2-4 mm, alternatively 2.5-3.5 mm, alternatively 2.8-3.2 mm, alternatively 2.9- 3.1 mm, alternatively 2.95-3.05 mm, alternatively 2.98-3.02 mm, alternatively 2.99-3.01 mm, alternatively 3 mm, or any sub-range or combination thereof.

[0046] Referring to FIG. 4, the oral fluid collector analysis aid 100 may further include a retention fitting 122 extending from the superior surface 106 of the isolation platform 102, the retention fitting 122 configured to receive and grip the applicator 16 to which the oral fluid collection absorbent substrate 18 is attached such that retraction of the applicator 16 from the sample tube 12 retracts the oral fluid collector analysis aid 100 from the sample tube 12. The retention fitting 122 may include at least one riser 124 extending from the superior surface 106 at the periphery 112 of the isolation platform 102, and the at least one riser 124 may include at least one angled projection 126 extending from the at least one riser 124 toward a center 128 of the isolation platform 102. The at least one riser 124 may include a plurality of the at least one angled projection 126. The retention fitting 122 may include a plurality of the at least one riser 124.

[0047] Referring to FIGS. 5A-5D, in an alternate further embodiment, the oral fluid collector analysis aid 100 further includes a standoff 118 extending from the superior surface 106 of the isolation platform 102, the standoff 118 including an extension 130 configured for insertion into a retention aperture 24 disposed in the cap 14 of the oral fluid collection assembly 10. The standoff 118 may have a length 120 sufficient to position the inferior surface 108 of the isolation platfomiAttorney Docket No.: 23619-0092-PCT102 at, near, on, or above the support ledge 42 of the lumen 30 while also still engaging with the retention aperture 24 of the cap 14.

[0048] The standoff 118 may have any suitable thickness 121, including, but not limited to a thickness 121 of 2-4 mm, alternatively 2.5-3.5 mm, alternatively 2.8-3.2 mm, alternatively 2.9-3.1 mm, alternatively 2.95-3.05 mm, alternatively 2.98-3.02 mm, alternatively 2.99-3.01 mm, alternatively 3 mm, or any sub-range or combination thereof. The standoff 118 may have any suitable length 120, depending on the distance between the cap 14 and the desired position of the isolation platform 102.

[0049] Referring to FIGS. 6A and 6B, in an alternative further embodiment, the oral fluid collector analysis aid 100 further includes at least one riser 124 extending from the superior surface 106 at a periphery 112 of the isolation platform 102. The at least one riser 124 may include a lateral extension 132 extending from the at least one riser 124 such that the end of the applicator 16 to which the oral fluid collection absorbent substrate 18 is attached (omitted here for clarity) may be advanced past the lateral extension 132 with the applicator in a first rotational orientation 134 and then rotated to a second rotational orientation 136 such that a superior surface 48 of the applicator 16 is in contact with the lateral extension 132.

[0050] Referring to FIGS. 7A and 7B, in an alternative further embodiment, the oral fluid collector analysis aid 100 further includes at least one riser 124 extending from the superior surface 106 at a periphery 112 of the isolation platform 102, the at least one riser 124 including at least one lateral extension 132 extending from the at least one riser 124, the at least one lateral extension 132 forming a friction-fit or snap-fit connector 138 configured for friction-fitting or snap-fitting, respectively, to a shaft 50 of the applicator 16 to which the oral fluid collection absorbent substrate 18 (not shown in figure) is attached.

[0051] Referring to FIGS. 2B, 3C, and 5D, in one embodiment, an oral fluid collection assembly system 1 includes an oral fluid collection assembly 10 including a sample tube 12 having a lumen 30, a cap 14 enclosing a sample tube aperture 26 disposed at a first end 20 of the sample tube 12, an applicator 16 extending from the cap 14 into the lumen 30, and an oral fluid collection absorbent substrate 18 extending from the applicator 16 within the lumen 30, and an oral fluid collector analysis aid 100 including an isolation platform 102 having lateral dimensions 104 sizedAtorney Docket No.: 23619-0092-PCTto be disposed within the lumen 30, the isolation platform 102 including a superior surface 106 facing the sample tube aperture 26 and an inferior surface 108 distal across the isolation platform 102 from the superior surface 106, wherein when the oral fluid collector analysis aid 100 is disposed within the lumen 30, the oral fluid collection absorbent substrate 18 contacts the superior surface 106 of the isolation platform 102 and the superior surface 106 of the isolation platform 102 is positioned above a maximum oral fluid solution level 44 of the lumen 30 such that an oral fluid solution 34 disposed within the lumen 30 is isolated from the oral fluid collection absorbent substrate 18. It is specifically intended that the oral fluid collection assembly system 1 may include any of the embodiments or variations disclosed herein with respect to the oral fluid collection assembly 10 and its component parts and features and with respect to the oral fluid collector analysis aid 100 and its component parts and features.

[0052] In one embodiment a method for extracting a representative oral fluid sample from an oral fluid collection assembly 10 includes receiving an oral fluid solution 34 in the oral fluid collection assembly 10, removing the cap 14, the applicator 16, and the oral fluid collection absorbent substrate 18 from the sample tube 12, inserting an oral fluid collector analysis aid 100 through the sample tube aperture 26 into the lumen 30, reintroducing the cap 14 and the oral fluid collection absorbent substrate 18 to the sample tube 12 such that the oral fluid collection absorbent substrate 18 contacts the superior surface 106 of the isolation platform 102 above the maximum oral fluid solution level 44 of the lumen 30, collecting the oral fluid solution 34 in a portion of the lumen 30 at a second end 22 of the sample tube 12, below the maximum oral fluid solution level 44 of the lumen 30 such that the oral fluid solution 34 is isolated from the oral fluid collection absorbent substrate 18, and then extracting the representative oral fluid sample from the oral fluid solution 34.

[0053] The oral fluid solution 34 may include, but is not limited to, oral fluid samples, buffers, reagents, any other relevant fluid to sample collection and preparation, or combinations thereof.

[0054] Reintroducing the cap 14 and the oral fluid collection absorbent substrate 18 to the sample tube 12 may further include reintroducing the applicator 16 to the sample tube 12, or theAttomey Docket No.: 23619-0092-PCTapplicator 16 may be separated from the oral fluid collection absorbent substrate 18 and omitted from rcintroduction into the sample tube 12.

[0055] Collecting the oral fluid solution 34 in the portion of the lumen 30 at the second end 22 of the sample tube 12 may include any suitable technique, including, but not limited to, centrifuging the oral fluid collection assembly 100 with the oral fluid collector analysis aid 102 disposed in the lumen 30. Centrifuging may be conducted at any suitable speeds, including, but not limited to, speeds above 25 Newtons (where 1 RPM = 0.01666667 Newtons).

[0056] Extracting the representative oral fluid sample from the oral fluid solution 34 may include removing the cap 14 from the sample tube 12 and inserting a pipette 46 through a channel 110 formed from the superior surface 106 of the isolation platform 102 through the isolation platform 102 to the inferior surface 108 of the isolation platform 102.

[0057] Referring to FIGS. 5A-5D, inserting an oral fluid collector analysis aid 100 through the sample tube aperture 26 into the lumen 30 may include replacing the applicator 16 extending from the cap 14 with the oral fluid collector analysis aid 100 extending from the cap 14.EXAMPLES

[0058] Testing was performed to evaluate the efficiency of using an oral fluid collector analysis aid 100 as described above (in particular as shown in FIG. 4 but without standoff 118) according to the methods described herein, in comparison to non-inventive standard techniques (including the squeegee method, low centrifugation fold, and the Porex serum filter) lacking the oral fluid collector analysis aid 100. It was observed that centrifuging an Abbott® Quantisal™ Oral Fluid Collection Device sponge dry using an oral fluid collector analysis aid 100 yields more analyte recovery and volume than techniques that leave the sponge in solution. It is further believed that the sponge and the bulk liquids are not at equilibrium regarding analyte concentrations, demonstrating the importance of the oral fluid collector analysis aid 100 and the presently disclosed methods.

[0059] For each test (performed in triplicate), 1 mL of oral fluid was collected with a collection sponge until the indicator turned blue and no liquid was left in the test tube. The collection sponge was placed in bulk liquid for four hours statically. “Spong Fold Cent” refers to collection sponge-Attorney Docket No.: 23619-0092-PCTfold low-speed centrifugation. “Manual Compression” refers to squeegeeing until no visual dripping occurs. “Porcx” refers to a Porcx scrum filter described in U.S. Patent Application Publication No. 2006 / 0245977 in FIGS. 8a and 8b. Liquid was transferred from the bottom of the oral fluid collection assembly to a graduated cylinder and the volume was recorded.

[0060] Table 1: Volume Recovery Comparison.Technique Volume of Oral Fluid Extracted (mL) Average Volume (mL)3.2Manual Compression 3.0 3.23.33.5Porex 3.4 3.43.23.4Sponge Fold Cent 3.4 3.43.33.9Inventive 4.0 3.93.9

[0061] Analyte recovery was assessed by reviewing peak area, analyte accuracy at 50 ng / mL and analyte precision at 50 ng / mL. Analyte was precisely spiked into negative synthetic oral fluid in a silanized test tube to a volume of 1 mb and mixed thoroughly. The resulting solution alsoAttorney Docket No.: 23619-0092-PCTserved as a control. Oral fluid was then collected with a collection sponge until the indicator of the sponge turned blue and no liquid was left in the test tube. The sponge was then placed in the oral fluid collection assembly with the bulk liquid for at least four hours. The proceeded was performed in triplicate, and a salt-assisted liquid-liquid extraction was performed on all samples.

[0062] Table 2 compares analyte accuracy of manual compression versus centrifugation. The data demonstrates that when using the manual compression technique 28 of the 31 analytes measured were greater than± 15% of the target value (50 ng / mL). This improved to just 6 analytes falling outside of the acceptable ± 15% window when using the inventive centrifugation technique.

[0063] Table 2: Analyte Accuracy Comparison for Manual Compression versus Centrifugation.ManualCompression CentrifugationAnalyte AVG % Diffto 50 AVG % Diffto 506-Acetylmorphine 40.17 19.67 54.83 -9.67 Alprazolam 37.90 24.20 49.67 0.67 Amphetamine 42.33 15.33 59.75 -19.50 B enzoy lecgonine 35.63 28.73 51.65 -3.30 Buprenorphine 28.70 42.60 39.27 21.47 Cannabidiol 21.37 57.27 31.35 37.30 Clonazepam 41.57 16.87 51.10 -2.20 Cocaine 38.10 23.80 51.77 -3.53 Codeine 41.90 16.20 52.60 -5.20 Delta-9-THC 11.67 76.67 12.85 74.30 Diazepam 37.53 24.93 55.30 -10.60 EDDP 44.53 10.93 55.37 -10.73 Fentanyl 36.33 27.33 49.15 1.70 Hydrocodone 42.30 15.40 54.83 -9.67 Hydromorphone 36.43 27.13 49.30 1.40 Ketamine 41.83 16.33 53.30 -6.60 Lorazepam 42.13 15.73 54.00 -8.00 LSD 35.63 28.73 47.03 5.93 MDA 42.57 14.87 54.03 -8.07 MDMA 41.53 16.93 53.93 -7.87 Methadone 38.40 23.20 51.60 -3.20 Methamphetamine 35.13 29.73 47.40 5.20Morphine 39.77 20.47 63.30 -26.60Atorney Docket No.: 23619-0092-PCTNorfentanyl 36.67 26.67 50.20 -0.40 Oxazepam 43.67 12.67 59.73 -19.47 Oxycodone 41.77 16.47 56.75 -13.50 Oxymorphone 36.87 26.27 54.73 -9.47 PCP 40.83 18.33 55.45 -10.90 Propoxyphene 38.63 22.73 45.80 8.40 Temazepam 37.43 25.13 54.10 -8.20Tramadol 39.13 21.73 55.25 -10.50

[0064] Table 3 compares analyte accuracy of using a Porex f ter versus an inventive oral fluid collector analysis aid 100. The data demonstrates that when using the Porex filter 15 of the 31 analytes had a lower % difference than the inventive oral fluid collector analysis aid 100 and 16 of the 31 analytes had a higher % difference than the inventive oral fluid collector analysis aid 100.

[0065] Table 3: Analyte Accuracy Comparison for the Porex Filter versus the Inventive Oral Fluid Collector Analysis Aid.Inventive OralFluid CollectorAnalyte Porex Average % Diffto 50 Analysis Aid % Diffto 50 6-Acetylmorphine 44.50 11 45.48 9.05 Alprazolam 46.08 7.85 45.73 8.55 Amphetamine 48.20 3.60 50.83 -1.65 Benzoylecgonine 46.68 6.65 51.75 -3.50 Buprenorphine 40.18 19.65 36.48 27.05 Cannabidiol 34.30 31.40 28.63 42.75 Clonazepam 55.10 -10.20 56.98 -13.95 Cocaine 40.53 18.95 44.20 11.60 Codeine 43.13 13.75 46.50 7.00 Delta-9-THC 29.90 40.20 25.53 48.95 Diazepam 43.23 13.55 42.88 14.25 EDDP 45.65 8.70 46.20 7.60 Fentanyl 45.10 9.80 45.80 8.40 Hydrocodone 45.95 8.10 47.18 5.65 Hydromorphone 46.80 6.40 47.08 5.85 Ketamine 47.83 4.35 50.73 -1.45 Lorazepam 50.23 -0.45 47.30 5.40LSD 36.35 27.30 35.25 29.5Atorney Docket No.: 23619-0092-PCTMDA 43.70 12.60 43.40 13.20 MDMA 44.60 10.80 45.53 8.95 Methadone 45.58 8.85 45.43 9.15 Methamphetamine 50.23 -0.45 56.28 -12.55 Morphine 39.53 20.95 40.90 18.20 N orfentanyl 42.63 14.75 44.48 11.05 Oxazepam 44.13 11.75 42.08 15.85 Oxycodone 49.70 0.60 50.88 -1.75 Oxymorphone 46.33 7.35 45.30 9.40 POP 46.65 6.70 48.98 2.05 Propoxyphene 39.90 20.20 41.00 18.00 Temazepam 42.25 15.50 44.18 11.65Tramadol 47.50 5.00 47.35 5.30

[0066] The inventive oral fluid collection analysis aid 100 showed analyte recovery commensurate with the Porex filter, but offered additional benefits including a higher volume recovery yield and a much quicker extraction when preparing larger batches of samples. Ease of use compared to the Porex filter was also noted throughout the process.

[0067] While the foregoing specification illustrates and describes exemplary embodiments, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the essential scope thereof. Therefore, it is intended that the invention not be limited to the particular embodiment disclosed as the best mode contemplated for carrying out this invention, but that the invention will include all embodiments falling within the scope of the appended claims.

Claims

Atorney Docket No.: 23619-0092-PCTCLAIMSWhat is claimed is:

1. An oral fluid collector analysis aid, comprising:an isolation platform having lateral dimensions sized to be disposed within a lumen of a sample tube of an oral fluid collection assembly, the isolation platform including:a superior surface arranged to contact an oral fluid collection absorbent substrate of the oral fluid collection assembly; andan inferior surface distal across the isolation platform from the superior surface.

2. The oral fluid collector analysis aid of claim 1, wherein the lateral dimensions are smaller than an interior width of a superior portion of the lumen and are larger than an interior width of a inferior portion of the lumen such that the oral fluid collector analysis aid is configured to rest upon a support ledge formed within the lumen by a transition between the superior portion of the lumen and the inferior portion of the lumen.

3. The oral fluid collector analysis aid of claim 1 , wherein the isolation platform includes at least one channel fomied from the superior surface of the isolation platform through the isolation platform to the inferior surface of the isolation platform, the at least one channel including a channel width sufficient to receive an analyte fluid transfer device.

4. The oral fluid collector analysis aid of claim 1, wherein superior surface includes sufficient surface area to prevent the oral fluid collection absorbent substrate from passing through or bypassing the isolation platform.

5. The oral fluid collector analysis aid of claim 1 , further including a standoff extending from the inferior surface of the isolation platform, the standoff having a length sufficient to position the superior surface of the isolation platform above a maximum oral fluid solution level of the lumen.

6. The oral fluid collector analysis aid of claim 1, further including a retention fitting extending from the superior surface of the isolation platform, the retention fitting configured to receive and grip an applicator to which the oral fluid collection absorbent substrate is attached such that retraction of the applicator from the sample tube retracts the oral fluid collector analysis aid fromAttorney Docket No.: 23619-0092-PCTthe sample tube.

7. The oral fluid collector analysis aid of claim 6, wherein the retention fitting includes at least one riser extending from the superior surface at a periphery of the isolation platform, and the at least one riser includes at least one angled projection extending from the at least one riser toward a center of the isolation platform.

8. The oral fluid collector analysis aid of claim 7, wherein the at least one riser includes a plurality of the at least one angled projection.

9. The oral fluid collector analysis aid of claim 7, wherein the retention fitting includes a plurality of the at least one riser.

10. The oral fluid collector analysis aid of claim 1, further including a standoff extending from the superior surface of the isolation platform, the standoff including an extension configured for insertion into a retention aperture disposed in a cap of the oral fluid collection assembly.

11. The oral fluid collector analysis aid of claim 10, wherein the standoff has a length sufficient to position the inferior surface of the isolation platform at or above a support ledge of the lumen.

12. The oral fluid collector analysis aid of claim 1, further including at least one riser extending from the superior surface at a periphery of the isolation platform, the at least one riser including a lateral extension extending from the at least one riser above the periphery of the isolation platform such that an applicator to which the oral fluid collection absorbent substatc is attached may be advanced past the lateral extension with the applicator in a first rotational orientation, and with the applicator rotated to a second rotational orientation a superior surface of the applicator is in contact with the lateral extension.

13. The oral fluid collector analysis aid of claim 1, further including at least one riser extending from the superior surface at a periphery of the isolation platform, the at least one riser including at least one lateral extension extending from the at least one riser, the at least one lateral extension forming a friction-fit connector configured for friction-fitting to a shaft of an applicator to which the oral fluid collection absorbent substate is attached.

14. The oral fluid collector analysis aid of claim 1, further including at least one riser extending from the superior surface at a periphery of the isolation platform, the at least one riser including at least one lateral extension extending from the at least one riser, the at least one lateral extensionAtorney Docket No.: 23619-0092-PCTforming a snap-fit connector configured for snap-fitting to a shaft of an applicator to which the oral fluid collection absorbent substatc is attached.

15. An oral fluid collection assembly system, comprising:an oral fluid collection assembly, including:a sample tube having a lumen;a cap enclosing a sample tube aperture disposed at a first end of the sample tube;an applicator extending from the cap into the lumen; and an oral fluid collection absorbent substrate extending from the applicator within the lumen; andan oral fluid collector analysis aid, including:an isolation platform having lateral dimensions sized to be disposed within the lumen, the isolation platform including:a superior surface facing the sample tube aperture; andan inferior surface distal across the isolation platform from the superior surface,wherein when the oral fluid collector analysis aid is disposed within the lumen, the oral fluid collection absorbent substrate contacts the superior surface of the isolation platform and the superior surface of the isolation platform is positioned above a maximum oral fluid solution level of the lumen such that an oral fluid solution disposed within the lumen is isolated from the oral fluid collection absorbent substrate.

16. A method for extracting a representative oral fluid sample from an oral fluid collection assembly, comprising:receiving an oral fluid solution in the oral fluid collection assembly, the oral fluid collection assembly including:a sample tube having a lumen, the oral fluid solution being disposed in the lumen;a cap enclosing a sample tube aperture disposed at a first end of the sample tube;an applicator extending from the cap into the lumen; andAtorney Docket No.: 23619-0092-PCTan oral fluid collection absorbent substrate extending from the applicator within the lumen;removing the cap, the applicator, and the oral fluid collection absorbent substrate from the sample tube;inserting an oral fluid collector analysis aid through the sample tube aperture into the lumen, the oral fluid collector analysis aid including:an isolation platform having lateral dimensions sized to be disposed within the lumen, the isolation platform including a superior surface facing the sample tube aperture and an inferior surface distal across the isolation platform from the superior surface;reintroducing the cap and the oral fluid collection absorbent substrate to the sample tube such that the oral fluid collection absorbent substrate contacts the superior surface of the isolation platform;collecting the oral fluid solution in a portion of the lumen at a second end of the sample tube such that the oral fluid solution is isolated from the oral fluid collection absorbent substrate; and thenextracting the representative oral fluid sample from the oral fluid solution.

17. The method of claims 16, wherein reintroducing the cap and the oral fluid collection absorbent substrate to the sample tube further includes reintroducing the applicator to the sample tube.

18. The method of claim 16, wherein inserting an oral fluid collector analysis aid through the sample tube aperture into the lumen includes replacing the applicator extending from the cap with the oral fluid collector analysis aid extending from the cap.

19. The method of claim 16, wherein collecting the oral fluid solution in the portion of the lumen at the second end of the sample tube includes centrifuging the oral fluid collection assembly with the oral fluid collector analysis aid disposed in the lumen.

20. The method of claim 16, wherein extracting the representative oral fluid sample from the oral fluid solution includes removing the cap from the sample tube and inserting a pipette through a channel formed from the superior surface of the isolation platform through the isolation platform to the inferior surface of the isolation platform.

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