Diagnostic test device with capillary groove

Abstract

The utility model discloses a diagnostic testing device with capillary grooves. A diagnostic test device for testing a biological or environmental sample is provided. In one aspect, the diagnostic test device includes a chamber configured to receive fluid from a sample preparation reservoir at a first section of the chamber and a plurality of spaced apart valleys along an inner surface of the at least one chamber. Each of the plurality of spaced apart valleys includes a curved cross-section and is configured to facilitate flow of the fluid toward a second section of the at least one chamber.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 486,945, filed on February 24, 2023, the entire contents of which are incorporated herein by reference. Technical Field

[0003] The present disclosure relates to optimizing the transfer of sample solutions within consumables for diagnostic testing, and in particular for nucleic acid diagnostic testing. More specifically, the present disclosure relates to apparatus and methods for optimizing the volume of sample solutions moved from a sample preparation reservoir to a portion of a diagnostic test reservoir configured to receive thermal and optical energy for detecting an analyte of interest in the sample solution. Background Art

[0004] Amplification of nucleic acids is important in many fields, including medical, biomedical, environmental, veterinary, and food safety testing. Example methods of nucleic acid amplification include polymerase chain reaction (PCR) amplification and isothermal amplification.

[0005] Nucleic acid amplification can produce a large number of copies of a target gene sequence in a test solution. As part of a test assay, a specific label can be designed to link to the target sequence. Once combined, the label can provide a detectable signal from the test solution, such as an optical signal. The change in the optical signal can include changes in the color, opacity, bioluminescence and / or fluorescence of the test solution. In the case of a fluorescent label beacon, each label molecule can be configured with a fluorescent quencher that is very close to the fluorescent atom or atomic arrangement. The label molecule can be configured so that when selectively bound to the target nucleic acid sequence, the quencher and the fluorophore are separated, and the fluorescent signal can then be detected by the action of the fluorophore. In this arrangement, the fluorescence intensity of the target solution indicates the relative amount of the target genetic material in the test solution. Then, the signal can be used to form the basis of a diagnostic test to determine the presence or absence of the target material or analyte of interest in the sample to be tested and its relative amount.

[0006] Two or more labels can be included in a single test well, and each test well can provide an optical output based on binding to a different target nucleic acid sequence. Different sensors, or sensors with two or more selective outputs, can be used in conjunction with the two or more labels. For example, in a dual channel system, two different fluorophores can be used, which can be detected by two different fluorescence sensors, and the two different fluorescence sensors are configured to detect the emission within the respective frequency range of each fluorophore. Thus, the two channels can be distinguished.

[0007] This method can be used to provide a control channel. In an example control channel, the test assay chemistry is configured so that if the test process is run correctly, the control target (e.g., synthetic nucleic acid sequence) should always be present. The output of the control channel can be used to confirm that the test process has been run correctly by the system and / or to confirm the validity of the test results obtained by other channels measured by the system. This method can be applied to test more than one target sequence in a single test well.

[0008] Multiple test wells can be used. Each well can run a different amplification chemistry and / or a different set of target markers. As described above, the control channel can be operated in one or more wells.

[0009] The consumable diagnostic test device implementing multiple test holes can be implemented.Consumable diagnostic test device can be a disposable, single-use device for the nursing market, wherein ease of use, simplicity and cost per consumable are important considerations.Consumable can be formed by polypropylene, and polypropylene is a plastic that is easy to mold to form a mass-produced component with high chemical resistance and is easy to obtain at a relatively low cost. Polypropylene also has a relatively low water vapor permeability, which can promote the long-term storage of dry reagents in polypropylene consumables. In the diagnostic test based on nucleic acid, elution lysis buffer (ELB) is generally provided as eluting sample from a sample collection device (such as a swab), and genomic material is released from the sample for molecular diagnostic testing. ELB is typically a water-based solution. Therefore, the characteristic high polarity of ELB can interact with the relatively low polarity polypropylene of consumable diagnostic test in a way that suppresses test performance. For example, due to the poor wettability of polypropylene, the droplets of ELB may adhere to the surface formed by polypropylene. As another example, ELB droplets that have adhered to the walls early in the reaction may subsequently fall to the bottom of the reaction chamber, changing the concentrations of reactants (including but not limited to analytes of interest and reagents) and potentially causing changes in detectable output. Therefore, there is a need to improve many aspects of consumable diagnostic tests, and in particular nucleic acid-based diagnostic tests that use aqueous solutions to extract and test nucleic acids of interest. Utility Model Content

[0010] In one non-limiting embodiment, a diagnostic test device is provided. The diagnostic test device includes a cartridge body and a diagnostic test reservoir, the cartridge body including a sample preparation reservoir, the diagnostic test reservoir coupled to the cartridge body. The diagnostic test reservoir includes at least one chamber, a plurality of spaced-apart valleys along an inner surface of the at least one chamber, the at least one chamber being configured to receive a fluid from the sample preparation reservoir at a first section of the at least one chamber. Each of the plurality of spaced-apart valleys includes a curved cross-section and is configured to facilitate flow of the fluid toward a second section of the at least one chamber.

[0011] The curved cross-section comprises a smooth arc. Each of the plurality of spaced-apart valleys may comprise three inflection points. Each of the plurality of spaced-apart valleys may comprise three curved portions. Each of the plurality of spaced-apart valleys may comprise two convex portions separated by a concave portion. The transition between the inner surface of the at least one chamber and the plurality of spaced-apart valleys comprises a rounded edge. A valley in the plurality of spaced-apart valleys may comprise a semicircular or semi-elliptical cross-sectional shape. The plurality of spaced-apart valleys may be separated by a planar portion of the inner surface of the at least one chamber.

[0012] A portion of the inner surface in the second section of the at least one chamber may form a continuous circumferential surface. A portion of the inner surface in the second section of the at least one chamber may form a continuously curved surface. The inner surface may form a closed perimeter in the at least one chamber. A portion of the inner surface may terminate in a smooth arc in the second section of the at least one chamber. A portion of the inner surface may be continuous between the first section of the at least one chamber and the smooth arc in the second section of the at least one chamber.

[0013] The at least one chamber may include a window region below ends of the plurality of spaced-apart valleys.The at least one chamber may include a window region that does not include a valley of the plurality of spaced-apart valleys.

[0014] A valley of the plurality of spaced-apart valleys may taper along a portion of its height. A valley of the plurality of spaced-apart valleys may taper beginning at a height between the first section and the second section. An end of a valley of the plurality of spaced-apart valleys may have a semicircular profile. An end of a valley of the plurality of spaced-apart valleys may have a tapered profile.

[0015] A first valley of the plurality of spaced-apart valleys may extend a first distance toward the second section of the at least one chamber, and a second valley of the plurality of spaced-apart valleys may extend a second distance toward the second section of the at least one chamber, the second distance being longer than the first distance. A valley of the plurality of spaced-apart valleys may have a cross-sectional shape in the first section of the at least one chamber that is different from a cross-sectional shape at an end of the valley.

[0016] In another non-limiting embodiment, a method for performing a diagnostic test using a diagnostic test device is provided. The diagnostic test device includes a sample preparation memory and a diagnostic test memory. The method includes dispensing a fluid from the sample preparation memory into at least one chamber of the diagnostic test memory, into a plurality of spaced-apart valleys along an inner surface of the at least one chamber. Each of the plurality of spaced-apart valleys includes a curved cross-section and is configured to facilitate flow of the fluid toward a section of the at least one chamber. The method also includes performing an amplification reaction in the at least one chamber. The method also includes detecting the presence or absence of an analyte of interest in the at least one chamber.

[0017] Detecting the presence or absence of the analyte of interest may include detecting a change in fluorescent emission indicative of a test result, the fluorescent emission exiting the at least one chamber through a portion of a wall of the chamber, the portion of the wall not including a valley of the plurality of spaced-apart valleys. The method may also include flowing a fluid along the plurality of spaced-apart valleys toward the segment of the at least one chamber.

[0018] The curved cross-section may include a smooth arc. Each of the plurality of spaced-apart valleys may include three inflection points. Each of the plurality of spaced-apart valleys may include three curved portions. Each of the plurality of spaced-apart valleys may include two convex portions separated by a concave portion.

[0019] The transition between the inner surface of the at least one chamber and the plurality of spaced-apart valleys may include rounded edges. A valley in the plurality of spaced-apart valleys may include a semicircular or semi-elliptical cross-sectional shape. The plurality of spaced-apart valleys may be separated by planar portions of the inner surface of the at least one chamber.

[0020] The embodiments provided herein include the following numbered embodiments:

[0021] 1. A diagnostic test device comprising:

[0022] a cartridge body including a sample preparation reservoir; and

[0023] A diagnostic test reservoir coupled to the cartridge body, the diagnostic test reservoir comprising at least one chamber, a plurality of spaced-apart valleys along an interior surface of the at least one chamber, the at least one chamber being configured to receive fluid from the sample preparation reservoir at a first section of the at least one chamber, each of the plurality of spaced-apart valleys comprising a curved cross-section and configured to facilitate flow of the fluid toward a second section of the at least one chamber.

[0024] 2. The diagnostic test unit of embodiment 1, wherein the curved cross-section comprises a smooth arc.

[0025] 3. The diagnostic test unit of embodiment 1 or 2, wherein each of the plurality of spaced-apart valleys comprises three inflection points.

[0026] 4. The diagnostic test unit of any one of embodiments 1 to 3, wherein each of the plurality of spaced-apart valleys comprises three curved portions.

[0027] 5. The diagnostic test unit of any one of embodiments 1 to 4, wherein each of the plurality of spaced-apart valleys comprises two convex portions separated by a concave portion.

[0028] 6. The diagnostic test unit of embodiment 1 or 2, wherein the transition between the interior surface of the at least one chamber and the plurality of spaced-apart valleys comprises a rounded edge.

[0029] 7. The diagnostic test device of any one of embodiments 1 to 6, wherein each valley of the plurality of spaced-apart valleys comprises a semi-circular or semi-elliptical cross-sectional shape.

[0030] 8. The diagnostic test unit of any one of embodiments 1 to 7 wherein the plurality of spaced-apart valleys are separated by planar portions of the interior surface of the at least one chamber.

[0031] 9. The diagnostic test device of any one of embodiments 1 to 8, wherein a portion of the interior surface in the second section of the at least one chamber forms a continuous circumferential surface.

[0032] 10. The diagnostic test device of any one of embodiments 1 to 9, wherein a portion of the interior surface in the second section of the at least one chamber forms a continuously curved surface.

[0033] 11. The diagnostic test unit of any one of embodiments 1 to 10 wherein the inner surface forms a closed perimeter in the at least one chamber.

[0034] 12. The diagnostic test unit of any one of embodiments 1 to 11 wherein a portion of the interior surface terminates in a smooth arc in the second section of the at least one chamber.

[0035] 13. The diagnostic test unit of embodiment 12, wherein a portion of the interior surface is continuous between the smooth arc in the first section of the at least one chamber and the second section of the at least one chamber.

[0036] 14. The diagnostic test unit of any one of embodiments 1 to 13, wherein the at least one chamber further comprises a window region below ends of the plurality of spaced-apart valleys.

[0037] 15. The diagnostic test unit of any one of embodiments 1 to 13, wherein the at least one chamber further comprises a window region that does not include a valley of the plurality of spaced-apart valleys.

[0038] 16. The diagnostic test device of any one of embodiments 1 to 15, wherein a valley of the plurality of spaced-apart valleys tapers along a portion of its height.

[0039] 17. The diagnostic test unit of embodiment 16, wherein a valley of the plurality of spaced-apart valleys tapers beginning at a height between the first segment and the second segment.

[0040] 18. The diagnostic test device of any one of embodiments 1 to 17 wherein ends of valleys of the plurality of spaced-apart valleys have a semicircular profile.

[0041] 19. The diagnostic test device of any one of embodiments 1 to 18, wherein ends of valleys of the plurality of spaced-apart valleys have a tapered profile.

[0042] 20. A diagnostic test device according to any one of embodiments 1 to 19, wherein a first valley of the plurality of spaced-apart valleys extends a first distance toward the second section of the at least one chamber, and a second valley of the plurality of spaced-apart valleys extends a second distance toward the second section of the at least one chamber, the second distance being longer than the first distance.

[0043] 21. The diagnostic test device of any one of embodiments 1 to 20, wherein a valley of the plurality of spaced-apart valleys has a cross-sectional shape in the first section of the at least one chamber that is different than a cross-sectional shape at an end of the valley.

[0044] 22. A method of performing a diagnostic test using a diagnostic test device, the diagnostic test device comprising a sample preparation memory and a diagnostic test memory, the method comprising:

[0045] dispensing a fluid from the sample preparation reservoir into at least one chamber of the diagnostic test reservoir, into a plurality of spaced-apart valleys along an interior surface of the at least one chamber, each of the plurality of spaced-apart valleys comprising a curved cross-section and configured to facilitate flow of the fluid toward a section of the at least one chamber;

[0046] performing an amplification reaction in the at least one chamber; and

[0047] The presence or absence of an analyte of interest in the at least one chamber is detected.

[0048] 23. A method according to embodiment 22, wherein detecting the presence or absence of the analyte of interest includes detecting a change in fluorescent emission indicative of a test result, wherein the fluorescent emission leaves the at least one chamber through a portion of a wall of the chamber, wherein the portion of the wall does not include a valley among the plurality of spaced-apart valleys.

[0049] 24. The method of embodiment 22 or 23, further comprising flowing a fluid along the plurality of spaced-apart valleys toward the section of the at least one chamber.

[0050] 25. The method of any one of embodiments 22 to 24, wherein the curved cross-section comprises a smooth arc.

[0051] 26. The method of any one of embodiments 22 to 25, wherein each of the plurality of spaced-apart valleys comprises three inflection points.

[0052] 27. The method of any one of embodiments 22 to 26, wherein each of the plurality of spaced-apart valleys comprises three curved portions.

[0053] 28. The method of any one of embodiments 22 to 27, wherein each of the plurality of spaced-apart valleys comprises two convex portions separated by a concave portion.

[0054] 29. The method of any one of embodiments 22 to 25, wherein the transition between the interior surface of the at least one chamber and the plurality of spaced-apart valleys comprises a rounded edge.

[0055] 30. The method of any one of embodiments 22 to 29, wherein a valley of the plurality of spaced-apart valleys comprises a semicircular or semi-elliptical cross-sectional shape.

[0056] 31. The method of any one of embodiments 22 to 30, wherein the plurality of spaced-apart valleys are separated by planar portions of the interior surface of the at least one chamber. BRIEF DESCRIPTION OF THE DRAWINGS

[0057] The above aspects and other features, aspects and advantages of the embodiments of the present disclosure will now be described in conjunction with various embodiments with reference to the accompanying drawings. The embodiments shown are exemplary only and are not intended to be limiting. Throughout the accompanying drawings, similar symbols generally identify similar components unless the context otherwise indicates.

[0058] Figure 1 An exploded view of components of an exemplary diagnostic test device according to the present disclosure is illustrated.

[0059] Figure 2A The diagram shows a dispensing cap. Figure 1 An exemplary diagnostic test device is provided.

[0060] Figure 2B Illustration with shipping cap Figure 1 An exemplary diagnostic test device is provided.

[0061] Figures 3A-3C Picture shows Figure 1-2B A view of the test container is shown.

[0062] Figure 3D The relationship between the capillary groove radius and the liquid contact angle according to an embodiment of the present disclosure is plotted.

[0063] Figure 3E A view of an exemplary test container that does not include a capillary groove is illustrated.

[0064] Figure 3F-3H Picture shows Figure 1-2B A view of the test container is shown.

[0065] Figures 3I-3J Illustrated are views of exemplary test containers according to embodiments of the present disclosure.

[0066] Figure 4A Picture shows Figure 1 A view of the cartridge body of the illustrated embodiment.

[0067] Figure 4B Picture shows Figure 4A A view of a cylindrical chamber of the illustrated embodiment.

[0068] Figure 4C Picture shows Figure 4A Cross-sectional view of a cylindrical chamber of the illustrated embodiment.

[0069] Figure 4D and Figure 4E Picture shows Figure 4A Cross-sectional view of the cartridge body of the illustrated embodiment.

[0070] Figure 4F Picture shows Figure 4AA side view of the cartridge body of the illustrated embodiment.

[0071] Figure 4G Shows Figure 4A A top view of the cartridge body of the illustrated embodiment.

[0072] Figure 4H Picture shows Figure 1 Magnified image of the test container.

[0073] Figure 5A Picture shows Figure 1 The dispensing cap.

[0074] Figure 5B Illustrated is a cross-sectional view of another dispensing cap according to the present disclosure.

[0075] Figure 5C Picture shows Figure 5B The distribution cap and Figure 1 A cross-sectional view of a cartridge body engagement of an embodiment.

[0076] Figure 5D Picture shows Figure 1 The locking tab of the dispensing cap is Figure 1 Interaction of the locking threads of the barrel body.

[0077] Figure 5E Picture shows Figure 1 The overtravel tab of the dispensing cap is Figure 1 Interaction of the barrier flange with the barrel body.

[0078] Fig. 6A Shows Figure 1 Side view of the dispensing mechanism.

[0079] Figure 6B Shows Figure 1 Angled bottom view of the dispensing mechanism.

[0080] Figure 6C and Fig.6D An alternative embodiment of a sealing member according to the present disclosure is shown.

[0081] Fig. 6E and Fig. 6F They are shown respectively Figure 6C and Fig.6D Top and bottom views of an alternative embodiment of a sealing member depicted in FIG.

[0082] Fig. 7A Picture shows Figure 1 A cross-sectional view of an embodiment of the present invention in which a dispensing mechanism has been inserted into a sample preparation reservoir.

[0083] Figure 7B Picture shows Figure 1A cross-sectional view of an embodiment in which the dispensing mechanism has pierced the seal.

[0084] Figure 7C Shows Figure 1 A cross-sectional view of an embodiment of the present invention wherein the sealing member has engaged the wall of the cylindrical chamber but has not pierced the seal.

[0085] Fig.7D and Fig. 7E Shows Figure 1 A cross-sectional view of an embodiment of Figure 1 In the embodiment of the present invention, the dispensing mechanism has been fully inserted and a predetermined amount of fluid has been dispensed into the diagnostic test reservoir. Fig.7D is Fig. 7E A closer view showing the piercing member, Fig. 7E The entire diagnostic test set is shown.

[0086] Figure 8 An example method for performing a diagnostic test using a diagnostic test device according to the present disclosure is illustrated.

[0087] Fig. 9 The diagram shows a portion of a diagnostic test device received in Figure 1 Diagnostic test device.

[0088] Figure 10-18 A diagram is shown of an exemplary diagnostic test device according to the present disclosure.

[0089] Figures 19A-19C An example of atomization or droplet formation in a device that does not include a capillary groove according to the present disclosure is illustrated. DETAILED DESCRIPTION

[0090] Embodiments of the present disclosure provide devices, systems and methods capable of optimizing the transfer of a solution (e.g., a sample solution) from a portion of a diagnostic test device to another portion of the device. The solution may include a high-polarity liquid, such as a water-based solution, and when the solution contacts or otherwise interacts with a surface (e.g., a plastic surface) formed by a low-polarity material, the high-polarity liquid tends to be retained on the surface. The surface may include, for example, the surface of a component formed by polypropylene, and when the solution is transferred in the diagnostic test device, the solution may pass through or along the surface. Embodiments of the present disclosure include surfaces with one or more capillary grooves. The capillary grooves are shaped and sized to facilitate the flow of the solution, such as downward flow. For example, an embodiment of a diagnostic test device including a capillary groove according to the present disclosure may advantageously reduce the tendency of a solution to produce droplets on a surface during transfer from a portion of the diagnostic test device to another portion of the device.

[0091] Using the embodiment of the capillary groove according to the present disclosure to reduce or eliminate the variable, uncontrolled and / or inefficient transfer of the solution can increase the volume of the solution received in the part where the test occurs in the diagnostic test device, thereby increasing the amount of the sample that can be used to measure the reaction. For example, the embodiment of the present disclosure can advantageously increase the volume of the solution transferred from the sample preparation storage to the test storage or a part of the test storage in the diagnostic test device, and deliver heat and / or light energy to perform diagnostic tests at this part of the test storage. Advantageously, using the embodiment of the present disclosure to increase the volume of the solution reliably and consistently delivered to the test storage can increase the amount of the analyte of interest included in the determination or other test reactions, which contributes to the diagnostic test results with higher accuracy and specificity. In addition, using the embodiment of the present disclosure to increase the volume of the solution reliably and consistently delivered to the test storage can ensure that the reagent (such as a dry reagent) in the test storage is reconstructed to the target concentration. For example, assuming that the desired volume of the solution is reliably and consistently delivered to the region where the reagent is reconstructed in the test storage, the embodiment of the present disclosure can allow the determination to be designed and / or optimized.

[0092] In many cases, the elution lysis buffer (ELB) used in the diagnostic test platform is a water-based solution. The consumables used in the diagnostic test - such as but not limited to the barrel, tube or reaction chamber - are usually formed of or include plastics such as polypropylene or polyethylene. The plastics (such as polypropylene and polyethylene) that are usually implemented are relatively low-polarity materials. Therefore, the characteristic high polarity of ELB may cause beading on the surface of the plastic parts of the consumables (such as the reaction chamber configured to receive the solution).

[0093] This interaction can result in less than the optimal amount of solution available for testing in a diagnostic test platform. For example, the ELB containing the collected patient sample can bead up and / or fog up on the relatively low polarity plastic (polypropylene in this non-limiting example) on the inner surface of the reaction chamber wall. Figures 19A-19CThis phenomenon is illustrated. For example, the test reservoir 1902 may include two reaction chambers 1910, each of which includes an inner surface 1912. Although some ELB solution 1906 may be dispersed to the bottom of the reaction chamber 1910, some ELB solution may be retained on the upper portion of the inner surface 1912, in the form of droplets 1908 and atomization 1904. In these embodiments, the volume of the ELB solution 1906 at the bottom of the reaction chamber 1910 is reduced because a portion of the ELB containing the collected patient sample is present in the droplets 1908 or atomization 1904 rather than in the volume of the ELB solution 106 at the bottom of the reaction chamber 1910. In some cases, the droplets 1908 may not participate in the reaction occurring at the bottom of the test reservoir 1902. In some cases, the droplets 1908 may adhere to the wall of the reaction chamber 1910, only to then fall to the bottom of the test reservoir 1902 when the reaction occurs, changing the concentration of the reagent in the ELB solution 1906 when the reaction is performed.

[0094] exist Fig.19A 1904. In the figure, the volume of ELB solution 1906 at the bottom of reaction chamber 1910 is reduced because the dispersed ELB is present in droplets 1908 and mist 1904. ELB can be dispersed from the top of reaction chamber 1910 and can fall or flow down to the bottom of chamber 1910. However, generally, some volume of ELB remains on the upper portion of surface 1912 of chamber 1910, as shown in the figure as mist 1904 and droplets 1908. Due to the unequal droplet formation and mist between the two chambers 1910, the volume of ELB solution 106 at the bottom of each chamber 1910 is unequal.

[0095] exist Fig.19B In FIG. 1 , a portion of the volume of the ELB solution distributed into the reaction chamber 1910 exists in the form of droplets 1908. The volume of the ELB solution 106 at the bottom of the chamber 1910 decreases in accordance with the volume of the droplets 1908. Fig.19B In the embodiment, the droplets are not of the same volume, and therefore the ELB solution 1906 at the bottom of each chamber 1910 is not equal. As shown, the droplet 1908 on the surface 1912 of the left chamber 1910 is larger than the droplet 1908 on the surface 1912 of the right chamber 1910, and therefore the volume of the ELB solution 1906 at the bottom of the left chamber 1910 is smaller than the ELB solution 1906 at the bottom of the right chamber 1910.

[0096] exist Fig.19CIn the embodiment of the present invention, since a portion of the ELB solution dispensed into the reaction chamber 1910 is present in the droplets 108 formed at the top corners of the reaction chamber 1910, the volume of the ELB solution 1906 at the bottom of the reaction chamber 1910 is reduced. The ELB solution can be dispensed from the top of the reaction chamber 1910 and can fall or flow downward to the bottom of the chamber 1910. However, the dispensed ELB solution often accumulates at the top corners, such as Fig.19C The geometry of the top corners of reaction chamber 1910 provides two surfaces to which droplets 1908 can adhere. The formation of droplets 1908 again reduces the volume of ELB solution 1906 present at the bottom of chamber 1910.

[0097] Droplet formation and / or atomization of ELB solution may lead to the change of the amount of ELB solution containing sample introduced into the bottom of reaction chamber, wherein there may be reagent for measuring reaction. Beading and / or atomization may also lead to the unexpected change of the amount of test sample that can be used for measuring reaction. This in turn may lead to the inaccuracy of measurement result, because the amount (for example, volume) of test sample that can be used for measuring reaction is not well controlled. In addition, beading and / or atomization may introduce the change of reagent concentration reconstructed in reaction chamber, thereby may lead to inconsistent or inaccurate measurement result. These variability problems may be particularly serious when sample is delivered from one storage to another storage (such as reaction chamber 1910) in the mode that ELB solution is exposed to the surface (such as the inner surface 1912 of reaction chamber 1910) formed by plastic.

[0098] In some cases, the sample present in the ELB solution may include genomic material. For example, beading and / or atomization of the ELB solution may affect the amount of available genomic material (such as DNA or RNA) introduced into the amplification reaction. For example, beading and / or atomization of the ELB solution may reduce the amount of genomic material present in the reaction chamber 1910 at the location where the amplification reaction occurs (e.g., the bottom of the reaction chamber 1910).

[0099] As described above, in addition to reducing sample variability, it may be desirable that the ELB dispensed volume is consistent to ensure that the lyophilized reagent in the reaction chamber is reconstituted to the target concentration. As an example, the beading and / or atomization that results in a reduction in the volume of the ELB solution ultimately delivered to the target location in the diagnostic test platform may cause the lyophilized reagent to be reconstituted at a higher concentration than expected. Therefore, the determination involving these lyophilized reagents may not be performed as expected (e.g., the determination may produce inaccurate or inconsistent results).

[0100] Embodiments of the present disclosure provide devices, systems, and methods for ensuring a more consistent ELB dispersion volume by minimizing or eliminating ELB beading on the inner surface of a target storage (e.g., a reaction chamber). For example, embodiments of the present disclosure provide capillary grooves that can promote droplet flow to the bottom of the reaction chamber within the reaction chamber. For embodiments in which 100 μL of a sample-containing fluid is dispersed into a diagnostic test storage, including a capillary groove can prevent 20-30 μL of the sample-containing fluid from being suspended on the wall of the diagnostic test storage. In other words, in these embodiments, the capillary groove increases the volume available for assay reactions by 20-30 μL.

[0101] Embodiments of the present disclosure provide devices, systems and methods for transferring a predetermined volume of solution (e.g., a fluid sample) from a portion of a diagnostic test device to another portion of the device in unison, while also avoiding contamination of the solution and the external environment. The fluid sample may include a test sample in a buffer solution. In some cases, when the fluid sample is transferred from the first portion of the device to the second portion, the fluid sample has been amplified. The first portion of the diagnostic test device may include a sample preparation memory, and the second portion of the diagnostic test device may include one or more test containers. For example, a predetermined amount of fluid sample may be transferred from the sample processing memory to one or more test containers including pre-stored amplification reagents. One or more test containers may include a surface having a capillary groove, the capillary groove being shaped and sized to facilitate the flow of the fluid sample (such as downward flow) to a portion of one or more test containers. For example, the capillary groove may facilitate the movement of the fluid sample to a portion of one or more test containers that delivers heat energy and / or light energy to perform a diagnostic test. The sample processing device may include a dual internal cylinder, and a predetermined amount of the fluid sample may be distributed to two test containers using a plunger by the dual internal cylinder. Advantageously, both test containers may include surfaces with capillary grooves, resulting in a predetermined volume of solution being reliably and consistently delivered to the portions of both test containers that perform the assay or test reaction. Prior to transferring the fluid sample, the test container is sealed from the external environment and the sample preparation reservoir, and is therefore protected from contamination. After the fluid sample is transferred, the test container remains sealed from the external environment. Advantageously, the external environment is not exposed to the fluid sample, which may include hazardous components.

[0102] The diagnostic test device of the present disclosure can dispense a predetermined amount of fluid sample while the sample receiving end of the sample preparation storage is sealed. For example, the action of twisting the cap engaged to the sample receiving end of the sample preparation storage also dispenses the fluid sample from the sample preparation storage to the test container. After dispensing the fluid sample, the cap can be locked to prevent contact with the sample preparation storage and the test container, protecting them from contamination. Additional fluid flow between the sample preparation storage and the test container is also prevented. The mechanism for dispensing the fluid sample while sealing the diagnostic test device is not complicated and involves the movement of a single component within the sample processing storage. In particular, the dispensing mechanism includes a plunger, which is configured to directly contact the inner surface of the sample processing storage when the plunger is translated within the sample preparation storage, and the piercing end of the plunger pierces one or more seals separating the sample preparation storage and the test container. Once dispensed, the fluid sample in the test container can be measured, for example, using an amplification reaction to determine the presence or absence of a target analyte. Advantageously, a diagnostic test device including a surface having capillary grooves according to the present disclosure can reliably dispense precise volumes of fluid samples from a single sample preparation reservoir into two or more test containers storing different reagents, thereby allowing multiple testing of a single sample.

[0103] Embodiments of the present disclosure provide devices, systems and methods for preparing test samples and subsequently testing test samples, such as by combining fluorescently labeled amplification. One embodiment includes a diagnostic test assembly (also referred to herein as a "tube") for use with a diagnostic test instrument to perform diagnostic tests on biological or environmental samples. This tube can be used with a diagnostic test device (also referred to herein as an "instrument"). As described herein, the tube is easy for users to operate without the need for the facilities of a general test laboratory.

[0104] Throughout the following description, various embodiments will be described with reference to exemplary embodiments of rapid, nucleic acid-based diagnostic systems that can test for a variety of diseases. As illustrative examples, the system can test for sexually transmitted infections (STIs), such as gonorrhea and chlamydia, and respiratory tract infections (RTIs), such as influenza A or B. The example system is targeted at the point of care (POC) market where ease of use, simplicity, CLIA exemption, and rapid result turnaround time (TAT) are considerations. However, it should be understood that any device, system, and method described herein can be applied to any other medical, forensic, or other applications.

[0105] The present disclosure relates to devices, systems and methods capable of amplifying nucleic acids in samples (e.g., isothermal amplification). Unless expressly to the contrary, in the case of using the term amplification herein, it is intended to cover any variant of amplification, including but not limited to isothermal amplification and PCR amplification (including real-time and quantitative PCR). It should be understood that the devices, systems and methods of the present disclosure are not limited to nucleic acid amplification, and can test whether there is any target of interest in the sample. It will also be understood that the devices, systems and methods of the present disclosure are not limited to processing or preparing samples before testing whether there is a target of interest in the sample.

[0106] Example Diagnostic Test Set

[0107] Reference now Figures 1 to 7E An exemplary diagnostic test device 100 according to the present disclosure is described.

[0108] Diagnostic test device 100 is implemented in the test system fast, based on nucleic acid, and this system can carry out automated molecular diagnostic test to detect various analytes of interest.Diagnostic test device 100 comprises the tube 106 that is configured to be inserted into the diagnostic instrument of test system.In a non-limiting example, tube 106 is a consumable plastic container.Tube 106 can be formed by injection molded plastics or any other suitable material.Tube 106 can comprise bar code, for example be presented at the bar code on the outer surface of tube 106, and diagnostic test equipment can scan this bar code to automatically identify the mensuration that will be added to the patient sample of tube 106.In this non-limiting example, mensuration comprises sample preparation mensuration and isothermal amplification mensuration for detecting nucleic acid of interest.User can input patient and / or sample information by the touch screen on instrument or by bar code scanning.

[0109] In addition to the cartridge 106, the diagnostic test device 100 also includes a dispensing mechanism 102 that is configured to communicate with the Figure 1 The cartridge 106 is docked as shown. The cartridge 106 may include a cartridge body 108, a test container 112, and one or more seals 110a and 110b. The diagnostic test device 100 may include a closure configured to close a first end 120 of the cartridge body 108. For example, the diagnostic test device may include a dispensing cap 114 and / or a shipping cap 116. The dispensing cap 114 may be coupled to the dispensing mechanism 102. The dispensing mechanism 102 may include one or more sealing members 104, such as an O-ring, a gasket, or a grommet. Figure 1 In a non-limiting embodiment, the one or more sealing members 104 include two O-rings. Figure 2A and Figure 2BAs shown, the dispensing cap 114 and the transport cap 116 are both configured to be attached to the first end 120 of the barrel body 108 to close or seal the first end 120. In one example, the transport cap 116 is configured to reversibly close or seal the first end 120, and the dispensing cap 114 is configured to irreversibly close or seal the first end 120. The barrel body 108 includes a sample preparation storage 202 and one or more columnar chambers 206. The barrel body 108 can form the sample preparation storage 108 and the one or more columnar chambers 206. The material (e.g., fluid) present in the sample preparation storage 202 and the one or more columnar chambers 206 can be enclosed in the barrel 108. The test container 112 includes one or more diagnostic test storages 204. The test container 112 can form one or more diagnostic test storages 204. For example, a material of a fluid is present in the one or more diagnostic test storages 204. The diagnostic test storage 204 can be enclosed in the test container 112.

[0110] The test container 112 of the cartridge 106 may be of any suitable shape and size. Figure 1 In the non-limiting embodiment of FIG. 7 , the test receptacles 112 include one or more tubes, wherein each tube forms a single diagnostic test reservoir 204. However, it should be understood that other configurations may be appropriately implemented.

[0111] Embodiments of diagnostic test devices, systems, and methods according to the present disclosure may include test containers 112 that minimize or eliminate retention of sample-containing fluid on the walls of test containers 112 where no assay or test reaction occurs (e.g., droplets are formed on the walls of test containers 112 where no assay or test reaction occurs). For example, heat and / or optical signals associated with assay reactions, such as for amplification and detection of nucleic acids, may be directed to the bottom of the diagnostic test storage 204, but not to the upper portion of the diagnostic test storage 204. Therefore, sample-containing fluid in droplets or atomization present in the upper portion of the diagnostic test storage 204 may not receive heat as expected. Similarly, sample-containing fluid present in droplets or atomization may not be properly positioned to receive and transmit optical signals (or other signals for detecting assay results). In addition, ensuring that the sample-containing fluid distributed to the diagnostic test storage 204 is consistently and reliably dispersed to the bottom of the diagnostic test storage 204 can reduce the variability of the assay results. Consistently and reliably distributing the sample-containing fluid to the bottom of the diagnostic test reservoir 204 can also ensure that sufficient sample material (e.g., genomic material) is available for the assay reaction to ensure a higher likelihood of accurate assay results. Thus, embodiments of the diagnostic test devices, systems, and methods disclosed herein can advantageously increase the amount of sample available for an assay reaction, which, in an exemplary embodiment, occurs within a volume of fluid received and / or collected at the bottom of the test container 112. Embodiments of the diagnostic test devices, systems, and methods disclosed herein can prevent and / or reduce the likelihood of fluid droplets adhering to the walls or interior surfaces of the test container 112 prior to a reaction and subsequently falling to the bottom of the reaction chamber as the reaction proceeds by reducing droplet formation on the walls or interior surfaces of the test container 112.

[0112] Figure 3A , 3B 3H illustrate a cross section of the test container 112 . Figure 3F is a top view of the test container 112 . Figure 3G is a bottom view of the test container 112 . Figure 4H A view of the test container 112 is also illustrated. An end 312 of the test container 112 is open and configured to receive a fluid, thereby allowing access to one or more diagnostic test reservoirs 204. The other end 314 of the test container 112 is a closed end. The end 314 may be the bottom closed end of one or more diagnostic test reservoirs 204. The end 314 is configured to collect a fluid.

[0113] The amplification of the analyte of interest can occur in the diagnostic test storage 204 of the test container 112. The barrel body 108 can be coupled to the diagnostic test storage 204, in which isothermal amplification and fluorescence detection can occur. When attached to the barrel body 106 by the seal 110a and / or 110b, one or more diagnostic test storages 204 are physically and fluidically separated from each other. The second end 118 opposite to the first end 120 of the barrel body 108 can be coupled to the end 312 of the test container 112. Other configurations can be appropriately implemented. For example, in another non-limiting embodiment, the barrel body 108 and the test container 112 are integrated in an integral structure. Amplification (such as but not limited to isothermal amplification) and detection (such as but not limited to fluorescence detection) of one or more analytes of interest can be carried out in one or more diagnostic test storages 204. The optical signal can be directed to one or more diagnostic test reservoirs 204, and the optical signal emitted from the one or more diagnostic test reservoirs 204 can be detected and associated with the presence, absence, and in some cases, the amount of one or more analytes of interest can be directed to the one or more diagnostic test reservoirs 204. The wall of the test container 112 can include plastic, such as polycarbonate and / or polypropylene or any other suitable material (such as but not limited to polyethylene). It may be desirable to select a transparent, substantially transparent, and / or non-opaque material to facilitate the transmission of the optical signal through the wall of the test container 112. The test container 112 can also include a lip 302 to facilitate attaching the test container 112 to the cartridge body 108 disclosed herein. The test container 112 can include one or more protrusions 310 located on or around the lip 302.

[0114] It should be understood that the present disclosure is not limited to test containers 112 having two diagnostic test reservoirs 204, such as Figure 1 , 3A 3C, 3E-3H, and 4H. For example, the test container 112 may be implemented with one diagnostic test memory 204. Alternatively, the test container 112 may be implemented with three, four, or more diagnostic test memories 204.

[0115] The test container 112 may include one or more capillary grooves 304. The capillary grooves 304 may facilitate the flow of dispensed liquid from the sample preparation reservoir 202 toward the bottom of the diagnostic test reservoir 204. In one example, the chamber 324 of the diagnostic test reservoir 204 is configured to receive fluid from the sample preparation reservoir at a first section 326 of the chamber 324. The capillary grooves 304 are configured to facilitate the flow of fluid toward a second section 330 of the chamber 324. Each capillary groove 304 may be a recess extending downwardly at least a portion of the height of the inner surface of the diagnostic test reservoir 204. In some embodiments, no portion of the capillary grooves protrudes into the interior space of the test container 112. Because each capillary groove 304 may be a recess in the inner wall of the diagnostic test reservoir 204, a test container 112 having one or more capillary grooves 304 may have a larger interior volume than a test container 112 without a capillary groove. Figure 3E An embodiment of a test container 112b having a diagnostic test reservoir 204b that does not include a capillary groove is depicted.

[0116] When viewed from above, Figure 3C As shown, the cross section of each capillary groove 304 may be semicircular and / or semi-elliptical. It should be understood that capillary grooves 304 having other cross-sectional profiles may be appropriately implemented in the embodiments of the present disclosure. Figure 3A-3B As shown in FIGS. 3H , some of the capillary grooves 304 may terminate substantially above the end 314 of the test container 112 and above the window region 308. One or more window regions 308 have substantially planar and / or flat walls with no, substantially no, or minimal optical interference due to the geometry of the test container 112 wall. One or more window regions 308 do not include any capillary grooves 304. Optical detection of an analyte of interest may involve transmission of an excitation signal and / or a detection signal through one or more window regions 308. In some embodiments, the blunt ends of one or more blunt-ended capillary grooves 318 may define the top of one or more window regions 308. The window region is located near the end 314 of the test container 112 and is spaced apart from the end 312 of the test container 112. In another embodiment, no capillary groove 304 extends to the end 314 of the test container 112. In yet another embodiment, all capillary grooves 304 extend to the end 314 of the test container 112.

[0117] Advantageously, some of the capillary grooves 304 extend to or near the end 314 to promote fluid flow down the entire height of the diagnostic test reservoir 204. In some embodiments, the total length of the capillary grooves 304 (e.g., the total distance that the capillary grooves 304 extend from the end 312 toward the end 314) can depend in part on the total volume of liquid dispensed into the diagnostic test reservoir 204. In order to promote the flow of fluid droplets toward the end 314, it may be desirable for the capillary grooves 304 to be able to transport these fluid droplets to at least the top surface of the fluid already at the end 314. Thus, as an illustrative example, if the volume of liquid dispensed into the diagnostic test reservoir 204 is substantially greater than half of the total volume of the diagnostic test reservoir 204, the capillary grooves 304 need not extend below approximately half of the height of the diagnostic test reservoir 204 because the top surface of the dispensed liquid will be above the lower end of the capillary grooves 304. Figure 3A-3B 3H, if 100 μL of fluid is dispensed into each diagnostic test reservoir 204, the top surface of the fluid will be higher than the top of the window area 308. Therefore, even a shorter blunt-end capillary groove 318 will extend through the top surface of the fluid. In some embodiments, one or more of the capillary grooves (e.g., tapered capillary groove 316) may taper as it approaches the end 314 of the test container. In some embodiments, one or more of the capillary grooves (e.g., blunt-end capillary 318) do not taper, but have a rounded blunt end 320 as it approaches the end 314. In some embodiments, at least one of the capillary grooves is a tapered capillary groove 316, and at least one of the capillary grooves is a blunt-end capillary groove 318. In a non-limiting example, near the end 312 of the test container 112, the width of the blunt-end capillary groove 318 may be about 0.5 mm. Until about the blunt end, the width of the blunt-end capillary groove may continue to be about 0.5 mm (e.g., not tapered). Blunt-ended capillary groove 318 may travel approximately 14 mm from the top of diagnostic test reservoir 204 to the top of window area 308. In embodiments where test container 112 is manufactured by injection molding, it may be desirable to taper capillary groove 304 to allow or assist in pulling test container 112 from the core of the injection mold.

[0118] In some embodiments, the width of the "tapered" capillary groove becomes smaller and / or decreases as the capillary groove approaches the end 314. For example, as shown by the arrows around the tapered capillary groove 316, the width of the capillary groove 316 is smaller near the end 314 of the test container 112. For example, the width W of the tapered capillary groove 316 is greater than the width w of the capillary groove 316 at a height closer to the end 314. In one non-limiting example, the width of the tapered capillary groove 316 can be about 0.5 mm near the end 312 of the test container 112. In some embodiments, the width W can be about 0.3 mm, and the width w can be less. The depth d of the tapered capillary groove 316 can also decrease as the tapered capillary groove 314 approaches the end 314. For example, near the end 312 of the test container 112, the depth d of the tapered capillary groove can be about 0.25 mm, corresponding to a capillary arc length a of about 0.64 mm. In some embodiments, the tapered capillary groove 316 does not taper along the entire length, but rather begins to taper at a height below the end 312. The tapered capillary groove 316 may include a taper across a distance L. In some embodiments, the tapered capillary groove 316 may begin to taper above the blunt end of the blunt end capillary groove 318. In some embodiments, the tapered capillary groove 316 begins to taper approximately at the height of the blunt end of the blunt end capillary groove 318. In some embodiments, the tapered capillary groove 316 may extend closer to the end 314 of the test container 112 than the blunt end capillary groove 318. The tapered capillary groove 316 may continue to extend to the end 314 of the test reservoir 204, or may terminate above the end 314 of the test reservoir 204.

[0119] Embodiments of capillary grooves according to the present disclosure may be shaped and sized to optimize the flow of liquid from a first reservoir (such as sample preparation reservoir 202) to a second reservoir (such as diagnostic test reservoir 204). For example, capillary grooves according to the present disclosure are sized to optimize the flow of liquid by capillary action or capillary action. The optimal size of the capillary configured to facilitate the flow of liquid depends in part on the properties of the liquid itself. Equation 1 describes the relationship between various parameters regarding the flow of a fluid droplet on a capillary groove:

[0120] 1.

[0121] where is the height of the liquid, T is the surface tension of the fluid, θ is the contact angle of the liquid with the capillary groove in radians, p is the density of the liquid, and g is the standard acceleration due to gravity (9.8 m / s 2 ), and r is the radius of the capillary groove. Figure 3D The relationship between the contact angle θ (in degrees) of the liquid and the radius r of the capillary groove is plotted in Figure 1 when other variables remain constant. Figure 3D, the height h is set to 15 mm, which is approximately the length from the end 312 of the test container 112 to the window area 308. Figure 3D , the surface tension T is assumed to be the surface tension of water at room temperature (0.072 dyne / m), and the density p is assumed to be the density of water at room temperature (997.77 kg / m 3 ). Assuming a particular height h and a fluid with properties similar to water at room temperature, the radius r and / or the contact angle θ can be selected for a particular application. In other words, the optimal capillary groove parameters can be advantageously selected for a particular use case. For example, if the contact angle θ a For a particular application, the optimal a In some embodiments of the test container 112 having a capillary groove with a height of 15 mm and assuming that the fluid has properties similar to water at room temperature, the capillary groove radius is 0.25 mm and corresponds to a liquid contact angle θ of approximately 76°. Figure 3D The capillary groove radius of 0.25mm and the contact angle of 76° are indicated by dotted lines. The capillary groove radius of 0.25mm may be desirable for use with room temperature water because it is not so small that it is difficult to manufacture, while producing a relatively high contact angle. High contact angle can promote the capillary action on the droplet better than low contact angle. For example, the parameters discussed above (for example, the radius r of the capillary groove) can be optimized to promote the flow of other liquids with properties different from water (for example, different viscosities, surface tensions and / or different densities). In addition, the number of capillary grooves included can be selected to optimize the fluid flow towards the end 314 of the diagnostic test storage 204. Typically, the inclusion of additional capillaries can further promote the fluid flow towards the end 314, and the reduction of the number of capillaries can reduce the fluid flow towards the end 314 and / or retain the area of ​​the wall of the test container 112 for transmitting signals (such as optical signals).

[0122] The test container 112 may include a detection tab 306. The detection tab 306 may help detect the presence or absence of a test container 112 received within the diagnostic test device. For example, the diagnostic test device may include a sensor, such as a mechanical sensor, configured to interact with the detection tab 306 of the test container 112. Inserting the test container 112 into the diagnostic test device may cause the detection tab 306 to press against the mechanical sensor of the diagnostic test device, thereby indicating that the test container 112 is properly seated within the diagnostic test device. Other configurations may be implemented as appropriate. For example, the diagnostic test device may include an optical sensor that emits an optical signal that is interrupted by the detection tab 306 when the test container 112 is properly seated. The detection tab 306 may include a "step-like" shape, such as Figure 4HThe test container 112 may also include a lip 430 to facilitate attachment of the test container 112 to the cartridge body 108, as described in more detail below.

[0123] One or more diagnostic test storages 204 may be preloaded with reaction components to run a specific diagnostic test. For example, one or more diagnostic test storages 204 may include freeze-dried reagents. Freeze-dried reagents may include enzymes, primers, probes, beacons, salts and / or other reagents for determining reactions. Mixed beads may also be included in one or more diagnostic test storages 204. Beads may be magnetic beads. Beads may be embedded in the pellets of freeze-dried reagents. When a fluid sample is introduced into one or more diagnostic test storages 204 and freeze-dried reagents are rehydrated, beads may promote the mixing of freeze-dried reagents with the fluid sample. For example, beads may move in one or more diagnostic test storages 204 under the influence of magnetic force to cause movement in any liquid in one or more diagnostic test storages 204 and help dissolve freeze-dried reagents. Beads may include stainless steel or any other suitable material. In alternative embodiments, one or more diagnostic test storages 204 may be preloaded with liquid reagents. In such embodiments, it may still be desirable to mix the preloaded liquid reagents with the fluid sample, such as by stirring the magnetic beads included in one or more diagnostic test storages 204. In some embodiments, one or more diagnostic test storages 204 may include one or more fins 322. The fins 322 may provide a gripping surface for the lyophilized reagent, thereby promoting adhesion of the lyophilized reagent to the bottom of the diagnostic test reservoir 204 .

[0124] Now refer to Fig. 3I and 3H Describing non-limiting examples of capillary grooves according to the present disclosure, Fig. 3I and 3H The diagram shows a top view and a cross section of a test container 112 of a diagnostic test device. In this non-limiting example, the above referenced Figures 3A-3C , 3F-3H, and 4H. The diagnostic test reservoir 204 includes a chamber 324 configured to receive fluid from a sample preparation reservoir at a first section 326 of the chamber 324. In this example, the capillary groove includes a plurality of spaced-apart valleys 328 along an inner surface of the chamber 324. The plurality of spaced-apart valleys 328 are configured to promote flow of the fluid toward a second section 330 of the chamber 324. The plurality of spaced-apart valleys 328 can be configured to inhibit droplets of the fluid from adhering to an inner surface in the first section 326 of the chamber 324 when the fluid is dispensed from the sample preparation reservoir into the chamber 324. The plurality of spaced-apart valleys 328 can be configured to increase the volume of the fluid collected in the second section 330 of the chamber 324.

[0125] Each of the spaced valleys 328 includes a curved cross section. The curved cross section may include a smooth arc a. The valleys in the plurality of spaced valleys 328 may include three inflection points P. The valleys in the plurality of spaced valleys 328 may include three curved portions C1, C2, and C3. The valleys in the plurality of spaced valleys 328 may include two convex portions CV separated by a concave portion CC. The transition between the inner surface of the chamber 324 and the plurality of spaced valleys 328 may include a rounded edge 332. The valleys in the plurality of spaced valleys 328 may include a semicircular or semi-elliptical cross-sectional shape. The plurality of spaced valleys 328 may be separated by a planar portion 334 of the inner surface of the chamber 324.

[0126] A portion of the inner surface in the second section 330 of the chamber 324 may form a continuous circumferential surface. A portion of the inner surface in the second section 330 of the chamber 324 may form a continuous curved surface. The inner surface may form a closed perimeter in the chamber 324. A portion of the inner surface may terminate in a smooth arc 342 in the second section 330 of the chamber 324. A portion of the inner surface may be continuous between the smooth arcs in the first section 326 of the chamber 324 and the second section 330 of the chamber 324.

[0127] The chamber 324 can include a window region 308 below the ends of the plurality of spaced-apart valleys 328. The window region 308 does not include a valley in the plurality of spaced-apart valleys 328.

[0128] A valley in the plurality of spaced-apart valleys 328 may taper along a portion of its height. The valley may taper beginning at a height between the first section 326 and the second section 330. An end 336 of a valley in the plurality of spaced-apart valleys 328 may have a semicircular profile 338. An end 336 of a valley in the plurality of spaced-apart valleys 328 may have a tapered profile 340. A first valley in the plurality of spaced-apart valleys 328 may extend a first distance toward the second section 330 of the chamber 324, and a second valley in the plurality of spaced-apart valleys 328 may extend a second distance toward the second section 330 of the chamber 324, wherein the second distance is longer than the first distance. A valley in the plurality of spaced-apart valleys 328 may have a cross-sectional shape in the first section 326 of the chamber 324 that is different from a cross-sectional shape at an end of the valley.

[0129] Figures 4A-4G 1 shows various aspects of a cartridge body 108 according to the present disclosure. Figure 4D As shown in the cross-sectional view of FIG. 1 , the cartridge body 108 includes a sample preparation reservoir 202 and one or more cylindrical chambers 206. The cartridge body 108 may also include a key 402, a threaded wall 404 at the first end 120, a lip 406 at the second end 118, a locking thread 412, and a blocking flange 428. The end 410 of the one or more cylindrical chambers 206 is also shown. Figure 4A and Figure 4D . The barrel body 108 may also include a lower surface 424 of the columnar chamber 206. The sample preparation storage 202 may be preloaded with reaction components to run a specific diagnostic test. For example, the sample preparation storage 202 may be preloaded with a certain volume of sample preparation fluid. The sample may be carried on a swab, which may be inserted into the sample preparation storage 202. The sample preparation storage 202 may include a sample preparation fluid to wash the sample from the swab into the sample preparation fluid, thereby producing a fluid sample in the sample preparation storage 202. The fluid sample in the sample preparation storage 202 may be configured to be processed to collect and / or concentrate nucleic acids, such as DNA and / or RNA. In some embodiments, the sample preparation fluid may include ELB. As an illustrative example, ELB may include red blood cell lysis buffer (RBCC), glycine electrophoresis buffer (GRBS) and / or sodium dodecyl sulfate solution (SDS). In an alternative embodiment, the sample preparation fluid does not need to be preloaded into the sample preparation storage 202, but may be loaded shortly before the sample is introduced.

[0130] Figure 4B Shown by Figure 4A The dashed rectangle in FIG. 1 represents a top cross-sectional view of the second end 118 of the cartridge body 108 . Figure 4C Shows from Figure 4A A side cross-sectional view as viewed through the dashed line 422 is shown in FIG.

[0131] The sample preparation storage 202 may have a fluid volume that is many times larger than the one or more diagnostic test storages 204. As an illustrative example, the sample preparation storage 202 may have a volume of about 6 mL, while the one or more diagnostic test storages 204 may contain a combined total fluid volume of about 400 μL. In some examples, the sample preparation storage 202 may hold a fluid volume between 0 and 5 mL, between 0.5 mL and 4.5 mL, between 1 mL and 4.0 mL, between 1.5 mL and 3.5 mL, between 2 mL and 3 mL, or any value or range within or limited by any of these ranges or values, although values ​​outside these values ​​or ranges may be used in some cases. Additionally or alternatively, in some examples, the sample preparation storage 202 may hold a fluid volume between 1 mL and 3 mL. The amount of sample preparation fluid actually held by the sample preparation storage 202 may depend on the specific assay.

[0132] The one or more diagnostic test reservoirs 204 are configured to receive a predetermined volume of a fluid sample from the sample preparation reservoir 202 by a process according to the present disclosure, including but not limited to the following reference Figure 8The example process described. One or more diagnostic test memories 204 can hold up to 50 μL of liquid, up to 75 μL of liquid, up to 100 μL of liquid, up to 150 μL of liquid, up to 200 μL of liquid, up to 250 μL of liquid, up to 300 μL of liquid, up to 350 μL of liquid, up to 400 μL of liquid, up to 450 μL of liquid, up to 500 μL of liquid, up to 1000 μL of liquid, or any value or range of fluid volumes within or limited by any of these ranges or values, although values ​​outside of these values ​​or ranges may be used in some cases. Additionally or alternatively, in some examples, one or more diagnostic test memories 204 can hold a fluid volume of 200 μL.

[0133] In some examples, the cartridge body 108 can include geometric structures that facilitate rapid heating of the contents of the sample preparation reservoir 202. For example, the cartridge body 108 can have a relatively high surface area to volume ratio, which can facilitate rapid heating, such as by having an elliptical cross-section. The walls of the cartridge body 108 can include a polypropylene material or any other suitable material (such as, but not limited to, polyethylene). Figures 4A-4G In the illustrated embodiment, the barrel body 108 transitions from having a circular transverse cross-section proximate the first end 120 to having an elliptical transverse cross-section in the lower interior portion of the barrel body 108. Figure 4D , Figure 4E and Figure 4G As shown, the inclined wall 426 of the barrel body 108 is a feature that transitions from a circular transverse cross section to an elliptical transverse cross section. At the portion of the inclined wall 246 closest to the first end 120, the transverse cross section is relatively circular, and becomes relatively elliptical as it approaches the cylindrical chamber 206.

[0134] Reference now Figure 5A and Figure 5B , the dispensing cap 114 includes a locking tab 502, an internal thread 504, an overtravel tab 506, a plug seal 508, and an inner ring 510 protruding from a flange 512. In this non-limiting embodiment, the inner ring 510 is a raised annular portion protruding from the inner surface of the flange 512. The flange 512 is configured to surround at least a portion of an end 606 of the dispensing mechanism 102 when the dispensing mechanism 102 is coupled to the dispensing cap 114. The inner ring 510 engages a corresponding ring 610 at the end 606 of the dispensing mechanism 102 in a manner that allows the dispensing cap 114 to freely rotate around the end 606 of the dispensing mechanism 102 when it is coupled to the dispensing mechanism 102. In an embodiment of the present disclosure, the dispensing cap 114 rotates around the longitudinal axis of the dispensing mechanism 102, even if the dispensing mechanism 102 remains stationary after being inserted into the cartridge body 108, as described more below.

[0135] In this non-limiting example, inner ring 510 and ring 610 are reversibly coupled via a flexible interference fit, allowing ring 610 to reversibly snap into and out of inner ring 510. It should be appreciated that other mechanisms for coupling dispensing cap 114 to dispensing mechanism 102 may be appropriately implemented.

[0136] The threaded wall 404 at the first end 120 of the cartridge body 108 can engage with a cap (e.g., a dispensing cap 114 or a shipping cap 116). In embodiments of the cartridge body 108 that include a locking thread 412, the locking thread 412 can also engage with a cap (e.g., a dispensing cap 114). Twisting the locking tab 502 of the dispensing cap 114 in a first direction (in this example, clockwise) causes the dispensing cap 114 to lock to the first end 120 of the cartridge body 108 through the locking thread 412, thereby inhibiting and / or preventing the dispensing cap 114 from moving in a second direction (in this example, counterclockwise) opposite to the first direction. Figure 5D The locking tab 502 is shown in a locked position, positioned against the locking threads 412. In the locked position, the dispensing cap 114 irreversibly engages the locking threads 412 such that a user cannot unscrew and disengage the dispensing cap 114 from the cartridge body 108. Advantageously, once the dispensing cap 114 is engaged to the locking threads 412, embodiments of the cartridge body 108 that include the locking threads 412 can completely seal a fluid sample within the device 100. This can prevent accidental contamination or leakage of the fluid sample 100 from the device 100 during or after performing a diagnostic test.

[0137] like Figure 5EAs shown, the blocking flange 428 of the barrel body 108 can engage the overtravel lug 506 of the dispensing cap 114. The blocking flange 428 can block the overtravel lug 506 from moving, thereby preventing or inhibiting the dispensing cap 114 from further rotating in the first direction (clockwise in this example). In some embodiments, when the dispensing cap 114 is in a position substantially the same as the engagement of the locking thread 412 with the locking lug 502, the engagement of the overtravel lug 506 with the blocking flange 428 occurs. That is, in some embodiments, once the dispensing cap 114 is twisted to the locked position, the locking thread 412 and the blocking flange 428 can each respectively engage the locking lug 502 and the overtravel lug 506, so that the dispensing cap 114 can neither be twisted counterclockwise nor clockwise. When engaged, the blocking flange 428 and the overtravel lug 506 prevent the rotational movement of the dispensing cap 114. When further rotational movement of the dispensing cap 114 is blocked and / or inhibited, translational movement of the dispensing cap 102 toward the end 410 of the barrel body 108 is also blocked and / or inhibited. Advantageously, embodiments of the present disclosure allow translational movement of the dispensing cap 102 toward the end 410 of the barrel body 108 to stop at a very precise predetermined distance from the end 410 of the barrel body, so that a precise predetermined volume of fluid is continuously dispensed from the sample preparation reservoir 202 to one or more diagnostic test reservoirs 204. In some non-limiting examples, another 7 to 10 degrees of rotation of the dispensing cap 114 in a clockwise direction (past the locked position) results in an additional 10 μL of fluid being dispensed from the sample preparation reservoir 202 to one or more diagnostic test reservoirs 204. In some embodiments, the additional 10 μL of dispensing is a 10% volume dispersion error. Therefore, embodiments of the present disclosure implementing the blocking flange 428 and the overtravel tab 506 can consistently deliver precise volumes of fluid to one or more diagnostic test reservoirs 204, thereby improving the reliability and accuracy of the test.

[0138] In some embodiments of the present disclosure, the barrel body 108 includes a feature advantageously positioned to improve the moldability and manufacturability of the barrel body 108. In a non-limiting example, the projection including locking thread 412 and blocking flange 428 of the barrel body 108 extends around less than half (e.g., about 170 ° of the circumference) of the circumference of the barrel body 108 tops. In some other embodiments, the projection can more or less surround the circumference of the top of the barrel body 108, such as 330 ° of the circumference or 45 ° of the circumference. In the embodiment where the barrel body 108 is a single molded plastic part, the projection of the circumference less than 180 ° surrounding the barrel body 108 can have better moldability. This is because, in such a non-limiting example, the projection on which the locking thread 412 and the blocking flange 428 are positioned does not cross the parting line used during manufacturing (e.g., during the injection molding process).

[0139] refer to Figure 5B and Figure 5C , the plug seal 508 of the dispensing cap 114 is an annular flange extending from the top inner surface of the dispensing cap 114. When in the locked position, the plug seal 508 can engage the first end 120 of the cartridge body 108. For example, the outer surface of the plug seal 508 can directly contact the inner surface of the first end 120 of the cartridge body 108, such as Figure 5C Plug seal 508 can prevent fluid within cartridge body 108 from leaving or leaking out of sample preparation reservoir 202 through first end 120. Additionally, plug seal 508 can prevent and / or inhibit fluid within sample preparation reservoir from contacting threaded wall 404 and / or threads 504. Thus, embodiments of the present disclosure implementing dispensing cap 114 with plug seal 508 can advantageously reduce or eliminate the risk that the external environment will be contaminated by fluid in sample preparation reservoir 202 (which may include pathogens).

[0140] In embodiments where the cartridge body 108 includes a key 402, the key 402 may engage a diagnostic test device. The key 402 may assist a user in properly orienting the cartridge 106 within the diagnostic test device. Additionally or alternatively, the key 402 may be sensed by the diagnostic test device to indicate insertion of the cartridge 106. Additionally or alternatively, in embodiments where each diagnostic test reservoir 204 is loaded with a different reagent (e.g., a lyophilized reagent), the key 402 may be used to orient the test container 112 so as to distinguish each diagnostic test reservoir 204.

[0141] The inner surface or wall 420 near the bottom of the cartridge body 108 may be shaped to define the sides of at least one chamber (e.g., cylindrical chamber 206). Figures 4A-4G In the illustrated embodiment, the sides of the cylindrical chamber 206 are formed by the inner surface 420. Although the cartridge body 108 of the illustrated embodiment includes two cylindrical chambers 206, other embodiments may include one or more cylindrical chambers 206. The cylindrical chamber 206 may include an opening 418. Such an opening facilitates the distribution of liquid from the sample preparation storage 202 to one or more diagnostic test storages 204. The opening 418 may be covered by a seal 110a. In some embodiments, each opening 418 may be covered by its own seal 110a, so that each opening 418 has a seal 110a.

[0142] It should be understood that the barrel body 108 of the present disclosure is not limited to Figure 1 -3. Figures 4A-4G and Figures 7A-7EThe cartridge body 108 may be implemented with one cylindrical chamber 206. Alternatively, the cartridge body 108 may be implemented with three, four, or more cylindrical chambers 206. The number of cylindrical chambers 206 of the cartridge body 108 may correspond to the number of diagnostic test reservoirs 204 of the test receptacles 112.

[0143] Seals 110a and 110b may include foil material and may be pierced by applying mechanical force. Seals 110a and 110b need not be the same material, but in some embodiments they may be the same material. Seals 110b may be fixed to test container 112 to cover the opening at the first end 434 of test container 112, thereby separating sample preparation storage 202 and one or more diagnostic test storages 204. In a non-limiting embodiment, when barrel body 108 and test container 112 are combined into single barrel 106, two seals 110a and 110b are pressed together. It may be desirable to attach seal 110b to the top of test container 112. In some embodiments where test container 112 holds a lyophilized reagent, for example, the attachment of seal 110b may ensure that moisture and / or other potential contaminants will not enter test container 112 before test container 112 and barrel body 108 are combined. Moisture and / or contaminants may cause inaccurate assay results, such as false positives or false negatives, in test container 112. When secured to the ends 410 of one or more cylindrical chambers 206, the seal 110a can retain fluids, such as liquid buffers, within the sample preparation reservoir 202 and the cylindrical chambers 206. As an illustrative example, the seal 110a can be attached to the underside of the cylindrical chamber 206 by heat sealing, and the seal 110b can also be attached to the top of the test container 112 by heat sealing.

[0144] In some embodiments, there may be only one seal 110. In such embodiments, the seal 110 may be attached to cover the opening 418 of the cylindrical chamber 206 before the test container 112 and the cartridge body 108 are combined, or the seal 110 may be attached to cover the first end 434 of the test container 112. In such embodiments, a single seal 110 may keep the fluid in the sample retrieval reservoir 202 separate from one or more diagnostic test reservoirs. Similarly, a single seal 110 may keep any lyophilized reagents within the diagnostic test reservoir 204 separate from the sample preparation reservoir 202.

[0145] In the example device 100, the cartridge body 108 is coupled to the test container 112 during manufacture and assembly of the device 100 prior to operation by an end user. Other embodiments may be implemented as appropriate. For example, in another non-limiting embodiment, the device 100 is formed of a single unitary structure including the cartridge body 108 integrally formed with the test container 112. In yet another non-limiting embodiment, the cartridge body 108 and the test container 112 are shipped separately to the end user, and the end user couples the cartridge body 108 and the test container 112 prior to operation.

[0146] The cartridge body 108 can be connected to the test container 112 using any number of coupling mechanisms, such as, but not limited to, a lip 406 that is matingly connected to a lip 430 on the outer surface of the test container 112. The sample preparation storage 202 and the one or more diagnostic test storages 204 with the seals 110a and / or 110b therebetween can be combined to form the cartridge 106. Thus, the seal 110a can define the bottom of the two cylindrical chambers formed by the inner surface 420. The seal 110b can define the top of the two diagnostic test storages 204. The combination of the sample preparation storage 202 and the one or more diagnostic test storages 204 and the seal 110a therebetween to form a single combined structure can be accomplished by, for example, ultrasonic welding, glue, snap connections, combinations of these, or any other suitable combination mechanism. It may be desirable for the sample preparation storage 202 and the one or more diagnostic test storages 204 to be sufficiently firmly combined to resist pressure buildup within the cylindrical chambers 206 and / or the one or more diagnostic test storages 204. In embodiments where the sample preparation reservoir 202 and the one or more diagnostic test reservoirs 204 are joined via ultrasonic welding, the test container 112 may include one or more protrusions 310. The one or more protrusions 310 may be spaced around the outer surface of the lip 430. The one or more protrusions 310 may help align the end 410 and lip 406 of the test container 112 against the second end 118 of the cartridge body 108 during ultrasonic welding. The one or more protrusions 310 may help center the test container 112 relative to the lip 406 of the second end 118 of the cartridge body 108 during ultrasonic welding. For example, the one or more protrusions may ensure that the test container 112 is approximately or substantially equidistant from the edge of the lip 406. The one or more protrusions 310 may thereby improve the consistency and / or strength of the ultrasonic weld.

[0147] 5 illustrates a dispensing cap 114 that can be coupled to a dispensing mechanism 102 according to an embodiment of the present disclosure. The dispensing cap 114 can include threads 504 configured to engage with the threaded wall 404 of the cartridge body 108. Additionally, in some embodiments, the dispensing cap 114 includes a locking tab 502 that can engage the locking threads 412 of the cartridge body 108. Once the locking tab 502 of the dispensing cap 114 has been rotated past the locking threads 412, further rotation in either direction can be prevented or inhibited, and the dispensing cap 114 can be locked to the cartridge body 108.

[0148] Fig. 6A and Figure 6B Aspects of the dispensing mechanism 102 are illustrated. The dispensing mechanism 102 includes a shaft 604, one or more piercing members 602, and one or more sealing members 104. In an embodiment of the present disclosure, the number of piercing members and sealing members 104 corresponds to the number of cylindrical chambers 206 and the number of diagnostic test reservoirs 204. Therefore, there is a one-to-one correspondence between the piercing members 602, the sealing members 104, the cylindrical chambers 206, and the diagnostic test reservoirs 204.

[0149] The shaft 604 and piercing member 602 of the dispensing mechanism 102 may include plastic. The plastic may be, for example, polycarbonate, acrylonitrile butadiene styrene (ABS), nylon, another thermoplastic, a polypropylene material, or any other suitable material (such as, but not limited to, polyethylene). The piercing member 602 may include a spike or other relatively sharp feature sufficient to pierce a seal (such as seal 110a). In one example, the piercing member 602 includes a spiked rod. Figure 6B As shown, the outer profile and cross-section of the piercing member 602 can be cross-shaped and / or plus-shaped. The piercing member 602 can include chamfered or beveled surfaces. For example, Fig. 6A and Figure 6B In a non-limiting embodiment, the cross-section of each piercing member 602 includes a chamfered surface 614. The cross and / or plus sign shape can facilitate fluid flow through the piercing member 602 and through the piercing seal 110a because the fluid can more easily flow through the concave surface of the piercing member 602, while the chamfered surface 614 continues to expand the opening. Advantageously, the cross or plus sign shape of the piercing member 602 can form an opening in the seal 110a that has a shape and size that facilitates the flow of fluid from the sample preparation reservoir 202 through the seal 110a. In a non-limiting example, the shape and size of the opening created in the seal 110a does not form an outlet or section of sealing material that can impede or block the passage of fluid through the opening.

[0150] In addition, the cross or plus sign shape of the piercing member 602 can advantageously allow air to exit the one or more diagnostic test reservoirs 204 and enter the sample preparation reservoir 202 before the opening is fully formed in the seal 110a. For example, air can pass through the concave surface of the piercing member 602, while the chamfered surface 614 continues to expand the opening. The pressure buildup in the one or more diagnostic test reservoirs 204 that would normally act to prevent fluid from flowing into the one or more diagnostic test reservoirs 204 can therefore be reduced as the opening is formed. This is particularly advantageous in the case where the air in the one or more diagnostic test reservoirs 204 is pressurized. It should be understood that the above-mentioned advantages of the embodiments of the piercing member 602 also apply to forming an opening in the seal 110b.

[0151] It should be understood that the allocation mechanism 102 of the present disclosure is not limited to Figure 1 and Figures 6A-7C Two piercing members 602 are shown. For example, the dispensing mechanism 102 can be implemented with one piercing member 602. Alternatively, the dispensing mechanism 102 can be implemented with three, four, or more piercing members 602. The number of piercing members 602 of the dispensing mechanism 102 can correspond to the number of cylindrical chambers 206 of the cartridge body 108.

[0152] The dispensing mechanism 102 can include one or more sealing members 104 , such as an O-ring, a gasket, or a grommet. The sealing member 104 can surround at least a portion of the piercing member 602 . Fig. 6A and Figure 6B An embodiment is shown where the sealing member 104 is an O-ring. Figure 6C-6F An alternative embodiment is shown in which the sealing member 104 is one or more washers. Fig. 6E and Fig. 6F 1 and 2 are top and bottom views of alternative embodiments of the sealing member 104. In a specific embodiment where the sealing member 104 is a gasket, as shown in FIG. Fig.6D As shown, the sealing member can be formed separately from the dispensing mechanism 102 and coupled to the dispensing mechanism 102 by pushing the gasket sealing member 104 onto the piercing member 602. In some embodiments, the gasket sealing member 104 can be overmolded onto the piercing member 602 during the manufacturing process of the piercing member 602. Figure 6C-6F In the non-limiting example of , the gasket is a unitary piece of material forming two channels 610, each channel 610 being configured to receive a piercing member 602. The gasket also includes two annular portions 612 separated by a distance.

[0153] In one example where the piercing member 602 includes a spiked rod, the sealing member includes a sealing member 104 surrounding the spiked rod. The sealing member 104 can be configured to directly contact the inner surface 420. In an embodiment where the sealing member 104 includes two O-rings, substantially the entire circumference of each O-ring can be in direct contact with the inner surface 420 of the cylindrical chamber 206 of the barrel body 108. In some cases, such as in Fig. 6A and Figure 6B In the non-limiting example shown in , each O-ring includes two annular portions separated by a certain distance. Substantially the entire circumference of each annular portion 612 can be in direct contact with the inner surface 420 of the cylindrical chamber 206 of the barrel body 108. In this case, the presence of two independent annular portions can form a two-piece seal against the inner surface 420, thereby providing redundancy in the event that one annular portion does not form an effective seal against the inner surface. In the case where the sealing member 104 includes a plurality of annular portions such as Figure 6C-6F In the embodiment of the gasket shown in , substantially the entire circumference of each annular portion 612 is in direct contact with the inner surface 420 of the cylindrical chamber 206 of the cartridge body 108. In such an embodiment, the presence of two separate annular portions 612 spaced apart can form a two-piece seal against the inner surface 420, thereby providing redundancy in the event that one annular portion 612 does not form an effective seal against the inner surface 420.

[0154] Sealing member 104 can include the elastic material that is applicable to form liquid impermeable or substantially liquid impermeable seal when being pressed against the material of barrel body 108.In some cases, sealing member 104 includes compressible material.In some non-limiting examples, sealing member 104 includes rubber, butyl rubber, thermoplastic vulcanizate (TPV) and / or thermoplastic elastomer (TPE).In some embodiments where sealing member 104 is an O-ring, sealing member 104 can include, for example, 70 Shore A butyl rubber.In some embodiments where sealing member 104 is a gasket (a gasket formed separately before being coupled to dispensing mechanism 102 or a gasket overmolded on dispensing mechanism), sealing member 104 can include 60 Shore A TPV.It should be understood that many other materials can be appropriately implemented according to the present disclosure.Dispensing cap 114 can be coupled to dispensing mechanism 102.For example, dispensing cap 114 can be coupled to dispensing mechanism 102 so that dispensing cap 114 can rotate around the longitudinal axis of dispensing mechanism 102. In one non-limiting embodiment, the end 606 of the dispensing mechanism 102 engages the inner ring 510 in the interior top surface of the dispensing cap 114 via a snap fit mechanism that allows the dispensing mechanism 102 to freely rotate relative to the dispensing cap 114 .

[0155] refer to Figure 4B and Figure 4C In embodiments having two or more cylindrical chambers 206, there may be a portion 414 of the interior surface that separates the two cylindrical chambers 206. The portion 414 of the interior surface between the two cylindrical chambers 206 may be formed to include a negative space, such as a notch 416. The notch 416 may at least partially define a predetermined volume of fluid dispensed from the sample preparation reservoir 202 to the one or more diagnostic test reservoirs 204. The depth of the notch 416 may thus be varied to adjust the predetermined volume dispensed from the sample preparation reservoir 202 to the one or more diagnostic test reservoirs 204.

[0156] The predetermined volume of fluid dispensed into the one or more diagnostic test reservoirs 204 is defined by at least three variables: the radius of the cylindrical chamber 206, the height H of the cylindrical chamber 206 measured between the lower surface 424 and the lowest point of the recess 416, and the volume displaced by the piercing member 602. Figure 4C The depth of the recess 416, represented by the distance D in FIG. 4, is inversely proportional to the predetermined volume dispensed because the depth of the recess 416 affects the height H at which the one or more sealing members 104 engage the inner surface between the two cylindrical chambers 206. Three non-limiting examples are described below to illustrate the effect of the recess 416 on the predetermined volume of fluid dispensed. For the purposes of these three examples, the only change in the dimension related to the predetermined volume of fluid dispensed is the depth D of the recess 416.

[0157] exist Figure 4B and Figure 4CIn the first non-limiting example shown in , for an embodiment in which a volume of about 100 μL of fluid is dispensed from each cylindrical chamber 206 to a corresponding diagnostic test reservoir 204, the depth D of the recess 416 is about 0.2 mm. In a second non-limiting example, the depth D of the recess 416 is about 0.1 mm, and a volume of fluid greater than about 100 μL is dispensed from each cylindrical chamber 206 to a corresponding diagnostic test reservoir 204. This is because, in this second non-limiting example, the depth D of the recess 416 is less than the depth D of the recess 416 in the first example. In other words, in the second example, the one or more sealing members 104 engage the inner surface between the two cylindrical chambers 206 at a height H greater than the height H in the first example, thereby enclosing a larger volume of fluid in the two cylindrical chambers 206. In a third non-limiting example, the depth D of the recess 416 is about 0.4 mm, and a volume of fluid less than about 100 μL is dispensed to one or more diagnostic test reservoirs 204. This is because, in this third non-limiting example, the depth D of the recess 416 is greater than the depth D of the recess 416 of the first example. In other words, in the third example, one or more sealing members 104 engage the inner surface between the two cylindrical chambers 206 at a height H less than the height H in the first example, thereby enclosing a smaller volume of fluid in the two cylindrical chambers 206. In some embodiments, the depth D of the recess 416 is between about 0 mm-2 mm, between about 0 mm-1.5 mm, between about 0 mm-1 mm, between about 0.1 mm-0.4 mm, but in some cases, other values ​​or ranges may be used. In a non-limiting example of the present disclosure, where approximately 100 μL of fluid is dispensed into each diagnostic test memory 204, the depth D of the recess 416 is between about 0.1 mm and about 0.4 mm.

[0158] In embodiments where the dispensing mechanism 102 includes two or more piercing members 602, the dispensing mechanism 102 may include a slot 608. The slot 608 is an empty space in the dispensing mechanism 102. The slot 608 may allow the one or more piercing members 602 and the one or more sealing members 104 to pass through the portion 414 of the inner surface between the two cylindrical chambers 206.

[0159] Figures 7A-7EFour different positions of the dispensing mechanism 102 within the sample preparation reservoir 202 during a dispensing operation according to the present disclosure are shown. The action involves movement of the dispensing mechanism 102 relative to the cartridge body 108 to break the seal 110a and / or the seal 110b, pushing a predetermined volume of fluid into one or more diagnostic test reservoirs 204. Advantageously, as the dispensing mechanism 102 translates along the longitudinal axis 108, embodiments of the devices, systems, and methods of the present disclosure dispense a predetermined volume of fluid when one or more sealing members directly contact the inner surfaces defining the sides of the sample preparation reservoir 202.

[0160] Fig. 7A The dispensing mechanism 102 inserted into the sample preparation storage 202 before the threaded wall 404 is engaged with the dispensing cap 114 is shown. By inserting the dispensing mechanism into the barrel body 108 as described above, the dispensing mechanism 102 can be manually placed in this position. Seals 110a and 110b are intact. As discussed, the dispensing mechanism 102 can be coupled to the dispensing cap 114. The dispensing cap 114 is configured to engage the threaded wall 404 of the sample preparation storage 202. The sealing member 104 is positioned above the cylindrical chamber 206 and therefore does not engage the cylindrical chamber 206. However, since the width of the sample preparation storage 202 is greater than its depth (i.e., the cross-section from top to bottom of the sample preparation storage is elliptical), the interior of the sample preparation storage 202 directs the dispensing mechanism 102 so that even when the piercing member 602 is positioned higher than the cylindrical chamber 206 in the barrel body 108, the piercing member 602 is also substantially aligned with the cylindrical chamber 206.

[0161] Figure 7B The dispensing mechanism 102 is shown after the dispensing mechanism 102 has pierced the seal 110a and / or the seal 110b. Fig. 7A The dispensing mechanism 102 may be in the position depicted in FIG. 1 after the threaded wall 404 engages the dispensing cap 114 and continues to twist the dispensing cap 114. Figure 7B As discussed, the dispensing cap 114 is coupled to the upper end 606 of the shaft 604 of the dispensing mechanism 102. This coupling allows the dispensing cap 114 to rotate freely relative to the shaft 604 and the piercing member 602. Therefore, the interaction of the threaded wall 404 and the thread 504 converts the torsion of the dispensing cap 114 into a vertical translational motion of the dispensing mechanism 102 along the longitudinal axis 108. When the cap 114 is tightened by twisting clockwise relative to the barrel body 108, the dispensing mechanism 102 translates downward. In this position, the dispensing cap 114 has not yet engaged the locking tab 502 and can still rotate relative to the dispensing mechanism 102 and the barrel body 108.

[0162] like Figure 7BAs shown, the dispensing mechanism 102 includes two sealing members 104 and two piercing members 602 configured to interact with the two cylindrical chambers 206 formed by the inner surface 420. When the dispensing cap 114 is screwed onto the barrel body 108 and twisted, the dispensing mechanism 102 translates downward, causing the piercing members to approach and then break the seals 110a and 110b. This translation forces the piercing member 602 to pass through the seal 110a.

[0163] There may be a pressure buildup below one or more sealing members 104 in one or more diagnostic test reservoirs 204 because any air in the diagnostic test reservoirs 204 is compressed as the dispensing mechanism 102 translates downward. The threaded wall 404 and the threads 504 may be configured to resist the upward force generated by this buildup of pressure. Once the dispensing cap 114 is locked with the locking threads 412, the interaction between the locking threads 412 and the dispensing cap 114 may also resist upward movement. In addition, the combination between the test container 112 and the cartridge body 108 should be sufficiently strong so that it will not break due to this buildup of pressure.

[0164] Figure 7C The dispensing mechanism 102 and cartridge body 108 are depicted shortly after the piercing member 602 pierces the seal 110a, but before the fluid travels into the one or more diagnostic test reservoirs 204. The sealing members 104 have engaged the inner surface 420 of the sealed chamber 206. The lower surface of each sealing member 104 has traveled below the notch 416, such that each sealing member 104 forms a complete seal with the inner surface 420 of the cylindrical chamber 206, thereby preventing or substantially preventing any fluid from flowing relative to the sealing members 104; that is, fluid cannot flow from below the sealing member 104 to above the sealing member 104, and fluid cannot flow from above the sealing member 104 downward to below the sealing member 104. Because the lowest point of the notch 416 defines a height at which the top plane of the cylindrical chamber 206 can be defined, the predetermined volume is not defined until the lower surface of the sealing member 104 passes just below the notch 416. At the instant that each piercing member 602 pierces the seal 110a, the predetermined volume (the shaded area) is defined by the inner surface 420 of the cylindrical chamber 206, the sealing member 104, the piercing member 602, and the seal 110a. As the dispensing mechanism 102 translates further downward, the sealing member 104 and the piercing member 602 force the predetermined volume to flow through the pierced seal 110a into the diagnostic test reservoir 204.

[0165] Once the predetermined volume is forced through the pierced seal 110a, the capillary grooves 304 of the one or more diagnostic test reservoirs 204 are configured to facilitate the flow of the predetermined volume. The capillary grooves 304 can facilitate the flow from the end 312 of the test container 112 toward the end 314 of the test container 112 so that the predetermined volume is collected at the location of the window area 308. In some embodiments, the capillary grooves 304 can facilitate the downward flow of the predetermined volume. The capillary grooves 304 can prevent and / or inhibit the predetermined volume from atomizing and / or droplets from adhering to the inner surface of the test container 112.

[0166] like Fig.7D and Fig. 7E As shown, the entire dispensing mechanism 102 translates downward relative to the cartridge body 108 until a predetermined volume (which is Fig. 7E 4 (depicted as the shaded area at the bottom of the diagnostic test storage 204 in the figure) has been completely and / or substantially dispensed into the diagnostic test storage 204. In some embodiments, when the dispensing cap 114 is locked, a certain volume of fluid may remain in the cylindrical chamber 206. In some embodiments, once the predetermined volume has been dispensed into the diagnostic test storage 204, the sealing member 104 can be flush with the lower surface 424 of the cylindrical chamber 206. In some embodiments, once the predetermined volume has been dispensed into the diagnostic test storage 204, the sealing member 104 is in direct contact with the lower surface 424 of the cylindrical chamber 206. The dispensing cap 114 is configured to lock on the locking threads 412 and the blocking flange 428 when the last predetermined volume is discharged from one or more cylindrical chambers 206. This inhibits and / or prevents the dispensing cap 114 from rotating relative to the barrel body 108 and the shaft 604, thereby preventing the dispensing mechanism 102 from further and / or reverse translational movement relative to the barrel body 108. These and other features may allow embodiments of diagnostic test reservoir 100 according to the present disclosure to accurately and consistently dispense not less than and not more than a predetermined volume of fluid into a diagnostic test reservoir.

[0167] Because the piercing member 602 and the sealing member 104 are locked in place as described above, the predetermined volume allocated to the one or more diagnostic test storages 204 is locked in the test container 112. The piercing member 602 and the sealing member 104 block the predetermined volume of fluid from the diagnostic test storage 204. In addition, because the piercing member 602 and the sealing member 104 are locked in place, additional fluid and other potential contaminants outside the diagnostic test device will not enter the one or more diagnostic test storages 204 or the sample preparation storage 202. As described below with reference to sample processing, the predetermined volume of fluid locked in the one or more diagnostic test storages can be subjected to processing, such as thermal processing and / or optical processing. Such processing can help produce a result indicating the presence or absence of one or more target analytes in the sample introduced into the diagnostic test device 100.

[0168] Sample processing using diagnostic test devices

[0169] Figure 8 An example process 800 for using the diagnostic device 100 according to the present disclosure is illustrated. The process may be implemented using the illustrated embodiment, for example Figure 1-7C and Fig. 9 The depicted embodiment, as well as other embodiments according to the present disclosure. In use, the barrel 106 is provided with a transport cap 116 that engages with the threaded wall 404 of the barrel body 108. The transport cap 116 is removed from the barrel body 108. For example, the instructions for use of the device 100 can instruct the user to loosen the transport cap 116 from the barrel body 108. At box 802, a swab is inserted into the sample preparation storage 202 of the barrel body 108 to deposit a sample. The instructions for use can instruct the user to rotate the tip of the swab in the sample preparation storage 202 according to a predefined protocol, such as rotating a specific number of revolutions and / or for a specific period of time.

[0170] It should be understood that the sample can be dispensed into the sample preparation storage 202 using any suitable method. For example, the sample can be dispensed directly into the sample preparation storage 202 without using a swab (e.g., by pipetting the sample). The liquid sample can include urine, blood, interstitial fluid, saliva, or any other suitable sample material. It should also be understood that embodiments of the present disclosure are not limited to liquid samples, and any suitable sample, including solid and gas samples, can be added to the sample preparation storage 202.

[0171] In this exemplary embodiment, the swab is then removed from the sample preparation storage 202 and discarded. The shipping cap 116 can then be screwed back onto the cartridge body 108. In another example, the shipping cap 116 is not screwed back onto the cartridge body 108.

[0172] The process next moves to block 804, where the cartridge 106 with the shipping cap 116 attached is inverted or otherwise agitated to mix the fluid sample, thereby dispersing the sample within the sample preparation fluid in the sample preparation reservoir 202. When the cartridge 106 is oriented so that the end 120 including the threaded wall 404 is facing upward (i.e., the cartridge 106 is not inverted), the fluid sample can be concentrated under the influence of gravity without air bubbles in the cylindrical chamber 206 of the sample preparation reservoir 202. After mixing, it may be desirable to have a pool of fluid sample without air bubbles in the cylindrical chamber 206 so that the desired volume of fluid can be dispensed into the sample preparation reservoir 202. In embodiments where the shipping cap 116 is not reengaged with the cartridge body 108, block 804 may include mixing the fluid sample without inverting the cartridge body 108.

[0173] In some examples, the sample preparation fluid can be heated before the swab is introduced and the sample is mixed into the sample preparation fluid. In other examples, the sample preparation fluid is heated after mixing with the sample. In embodiments where the sample is added directly to the sample preparation reservoir 202, the sample can be added before or after the sample preparation solution is heated. If particles containing the analyte of interest are present in the sample, the particles containing the analyte of interest can be dissolved in the solution by the chemical action of the sample preparation fluid and / or the elevated temperature.

[0174] The process next moves to frame 806, in which the barrel 106 is inserted into the diagnostic test device. The sample in the sample preparation fluid is then processed. The shipping cap 116, if present, can be removed before or after the barrel 106 is placed in the diagnostic test device. The shipping cap 116 does not include a locking tab for engaging the locking threads 412 of the barrel body 108, and therefore cannot be locked to the barrel body 108 like the dispensing cap 114.

[0175] The process next moves to block 808 where the dispensing mechanism 102 is inserted into the sample preparation reservoir 202. The dispensing mechanism 102 is vertically lowered through the sample preparation reservoir 202 toward the seal 110a such that each piercing member 602 and sealing member 104 is aligned or substantially aligned with a corresponding cylindrical chamber 206. As the dispensing mechanism 102 is lowered into the sample preparation reservoir 202, fluid can flow around and through the dispensing mechanism 102.

[0176] The process then moves to block 810 where the dispensing cap 114 of the dispensing mechanism 102 engages the sample preparation reservoir 202 , in this example, the threaded wall 404 of the sample preparation reservoir 202 .

[0177] Once the dispensing cap 114 has been lowered a certain distance along the threaded wall 404, the dispensing mechanism 102 will be in Figure 7C The position shown. The sealing member 104 engages the top of the two cylindrical chambers 206 formed by the inner surface 420 of the sample preparation storage 202. When the sealing member 104 engages the top of the two cylindrical chambers 206, the piercing member 602 is located above the seal 110a, which separates the sample preparation storage 202 and one or more diagnostic test storages 204. The inner surface 420, the seal 110a, the sealing member 104 and the piercing member 602 together define a predetermined volume of fluid. In the illustrated embodiment, these features define a predetermined volume of fluid separated by two fluids, each volume being associated with one of the two cylindrical chambers 206. The sealing member 104 forms a fluid seal with the inner surface 420, thereby trapping (one or more) predetermined volumes of fluid. After the sealing member 104 engages the inner surface 420, the fluid above the sealing member 104 present in the sample preparation storage 202 cannot enter the two cylindrical chambers 206.

[0178] In some examples, the predetermined volume of fluid sealed in each column chamber 206 is up to 10 μL of liquid, 25 μL of liquid, up to 50 μL of liquid, up to 70 μL of liquid, up to 75 μL of liquid, up to 100 μL of liquid, up to 125 μL of liquid, up to 130 μL of liquid, up to 150 μL of liquid, up to 200 μL of liquid, up to 250 μL of liquid, up to 300 μL of liquid, up to 350 μL of liquid, up to 400 μL of liquid, up to 450 μL of liquid, up to 500 μL of liquid, up to 1000 μL of liquid, or any value or range within or limited by any of these ranges or values, although values ​​outside of these values ​​or ranges may be used in some cases. Additionally or alternatively, in some examples, the predetermined volume of fluid is approximately 100 μL of liquid.

[0179] The dispensing cap 114 is then further rotated to translate the dispensing mechanism 102 to reach Figure 7B The piercing member 602 has pierced the seals 110a and 110b between the sample preparation reservoir 202 and the one or more diagnostic test reservoirs 204. Further translation causes the sealing member 104 to slide along the inner surface 420 of the sample preparation reservoir 202, acting as a piston that forms a sliding seal with the two cylindrical chambers 206 of the sample preparation reservoir 202. For example, due to the close fit between the sealing member 104 and the inner surface 420 inside the two cylindrical chambers 206 of the sample preparation reservoir 202, a liquid-tight seal can be formed between the sealing member 104 and the inner surface 420.

[0180] The method next moves to box 812, in which the seals 110a, 110b are pierced and a predetermined volume of fluid is pushed from within the cylindrical chamber 206 into the diagnostic test reservoir 204 by the downward movement of the dispensing mechanism 102. This dispensing action forces the predetermined volume of fluid into the diagnostic test reservoir 204. The seals 110a, 110b ensure that there is no fluid communication between the sample preparation reservoir 202 and one or more diagnostic test reservoirs 204 until the dispensing action. Once the sealing member 104 forms a seal with the inner surface 420, the fluid in the sample preparation reservoir above the sealing member 104 will not be dispensed into the one or more diagnostic test reservoirs 204. Therefore, in embodiments of the systems and methods of the present disclosure, a first portion of the total fluid volume present in the sample preparation reservoir 202 is dispensed into the diagnostic test reservoir 204, while a second portion of the total fluid volume present in the sample preparation reservoir 202 is not dispensed into the diagnostic test reservoir 204. In certain embodiments, where there are two cylindrical chambers 206, each cylindrical chamber 206 is capable of dispensing approximately 100 μL, the volume of fluid in the sample preparation reservoir 202 may be 500 μL or more. In certain embodiments with two cylindrical chambers 206, each cylindrical chamber 206 is capable of dispensing approximately 100 μL, the sample preparation reservoir 202 may have between 1 mL and 3 mL of fluid. In some embodiments, the total volume of fluid present in the sample preparation reservoir 202 is 1-300 times the volume of the predetermined volume dispensed to the diagnostic test reservoir 204. In some embodiments, the total volume of fluid present in the sample preparation reservoir 202 is 5-50 times the volume of the predetermined volume dispensed to the diagnostic test reservoir 204.

[0181] As described above, the diagnostic test reservoir 204 includes one or more capillary grooves 304 configured to facilitate a predetermined volume of fluid to flow from one end of the diagnostic test reservoir 204 (e.g., the end 312 of the test container 112) to the other end of the diagnostic test reservoir 304 (e.g., toward the end 312 of the test container 112). Ensuring that a constant volume of fluid is dispensed into the diagnostic test reservoir 204 can reduce the variability of the assay results. The constant and reliable dispersion of the fluid volume to the bottom of the diagnostic test reservoir can also ensure that sufficient sample material (e.g., genetic material) is available for the assay reaction to ensure a higher probability of accurate test results. Therefore, in an embodiment of the present disclosure, block 812 includes moving fluid along the one or more capillary grooves 304 from the first end 434 toward the bottom 436 of the test container 112.

[0182] In this non-limiting example of the present disclosure, one or more diagnostic test reservoirs 204 include two receiving chambers that together form a test container 112. Each receiving chamber of the test container 112 is configured to align with a cylindrical chamber 206 of the sample preparation reservoir 202. The diagnostic test reservoir 204 can be heated to perform an amplification reaction in the fluid dispensed into the diagnostic test reservoir 204. An optical fluorescent signal from the diagnostic test reservoir 204 can be detected through the wall of the test container 112.

[0183] In a non-limiting embodiment of the present disclosure, the dispensing mechanism 102 is free to move along the longitudinal axis of the sample preparation reservoir 202 until the point where the locking tab engages the locking thread, as described in further detail below. As the dispensing mechanism 102 is lowered along the longitudinal axis of the sample preparation reservoir 202, the fluid in the sample preparation reservoir 202 flows relative to the dispensing mechanism 102. In a non-limiting example of the present disclosure, the dispensing mechanism 102 and the dispensing cap 114 are the only movable parts of the diagnostic test device 100 during user operation. The entire dispensing mechanism 102 translates downwardly along the longitudinal axis of the diagnostic test reservoir 204 in a single motion until the translation of the entire dispensing mechanism 102 stops as described above. The downward movement of the dispensing mechanism 102 first defines a predetermined volume of fluid defined by the inner surface 420 of the sample preparation reservoir 202, the piercing member 602 of the dispensing mechanism 102, the sealing member 104 of the dispensing mechanism 102, and the seal 110a. Additional downward movement of the dispensing mechanism 102 then pierces the seals 110a, 110b with the piercing member 602. Further downward movement of the dispensing mechanism 102 ultimately dispenses the predetermined volume of the fluid sample into the diagnostic test reservoir 204 through the piston action of the dispensing mechanism in conjunction with the seal formed by the sealing member 104. A predetermined volume of the fluid sample is thereby dispensed into a single diagnostic test reservoir 204.

[0184] While the dispensing mechanism 102 moves downward along the longitudinal axis of the sample preparation storage 202, the rotation of the dispensing cap 114 about the longitudinal axis of the sample preparation storage 202 causes the locking threads 412 of the barrel 106 to engage with the locking tabs 502 of the dispensing cap 114. During the last rotation of the cap 114 to pierce the seals 110a, 110b, the locking tabs 502 on the dispensing cap 114 rotate beyond the ends of the locking threads 412. The locking threads 412 then substantially prevent and / or inhibit the rotational movement of the dispensing cap 114 in either direction, which in turn substantially prevents and / or inhibits the translational movement of the dispensing mechanism 102. It may be desirable that the locking threads 412 lock to the top of the barrel 106 so that the fluid in the sample preparation storage 202 remains sealed during and after the test operation. In addition, embodiments of the locking mechanism according to the present disclosure can advantageously lock the dispensing mechanism 102 in place to prevent any further movement of liquids and / or reagents between the sample preparation storage 202 and the diagnostic test storage 204.

[0185] In the devices, systems and methods according to the present disclosure, the dispensing mechanism 102 is an integral, one-piece structure that is the only movable component within the sample preparation reservoir 202, thereby reducing the possibility of alignment errors during sealing the sealing member 104 and dispensing the fluid into the diagnostic test reservoir 204. In the embodiment of the present disclosure, the sealing member 104 is easily aligned and reliably disposed within the two cylindrical chambers 206. There is a single stroke motion that causes the dispensing mechanism 102 to translate downward, thereby causing the dispensing action. Advantageously, the consistent and reliable sealing of the sealing member 104 during the dispensing action helps to dispense a consistent and accurate sub-volume of the fluid in the sample preparation reservoir 202 into the diagnostic test reservoir 204. This can advantageously contribute to more consistent and more accurate testing of the presence, absence or amount of an analyte of interest in the fluid to be dispensed into the diagnostic test reservoir 204.

[0186] The method next moves to box 814, in which the predetermined volume of fluid dispensed into the diagnostic test reservoir 204 can rehydrate the lyophilized reagent (if present in the diagnostic test reservoir 204). As described above, embodiments of the present disclosure may include a test container 112 having one or more capillary grooves 304, which can advantageously increase the volume of fluid that rehydrates the lyophilized reagent (if present) in the diagnostic test reservoir 204. The combination of the predetermined volume of fluid and the rehydrated reagent in the diagnostic test reservoir 204 is referred to herein as an amplification fluid. It should be understood that embodiments of the present disclosure are not limited to using dispensed fluid to rehydrate the reagent, or even to providing the reagent in the diagnostic test reservoir 204. Therefore, in some non-limiting embodiments, the composition of the fluid dispensed into the diagnostic test reservoir 204 is the same as the fluid composition tested for the presence, absence, or amount of the analyte of interest in the diagnostic test reservoir 204. According to the present disclosure, the fluid and the rehydration reagent in the diagnostic test reservoir 204 can be mixed. In some embodiments, beads (e.g., magnetic beads) included in the lyophilized reagent may be agitated to facilitate mixing of the diagnostic test reservoir 204. In such embodiments, mixing using beads may continue while the reaction is performed according to block 816, or while detection occurs according to block 818.

[0187] Once the reagents have been rehydrated, the method moves to frame 816, in which a reaction is performed in the amplification fluid in the diagnostic test storage 204. The reaction may include an amplification reaction. The reaction may include an assay. The reaction may involve applying heat to the diagnostic test storage 204, which is transferred into the fluid to promote an isothermal amplification reaction. In other cases, the amplification reaction includes cyclic heating to perform the amplification reaction. It should be understood that these exemplary reactions and assays are not restrictive, and any suitable reaction may be performed in the fluid in the diagnostic test storage 204.

[0188] The method ends at box 818, where the presence or absence of an analyte of interest is detected. The analyte of interest can be detected when the amplification reaction is carried out (e.g., during a real-time PCR test) or when the amplification reaction terminates. For example, the presence or absence of an analyte can be detected by a fluorescent signal generated during the amplification reaction. Advantageously, embodiments of the present disclosure including a test container 112 with one or more capillary grooves 304 can detect the presence, absence, and in some cases the amount of an analyte of interest with greater specificity and / or sensitivity.

[0189] Method for using a diagnostic test apparatus with a diagnostic test device

[0190] In some examples, before or after a dispensing action as described herein occurs, a diagnostic test device 100 can be introduced into a diagnostic test device 900. The device can be inserted into one or more heating blocks 902, 904 of the diagnostic test device 900. The diagnostic test device 900 is configured to accept a diagnostic test device 100. A diagnostic test device 100 with a shipping cap 116 or a dispensing cap 114 can be inserted into the diagnostic test device 900.

[0191] In a non-limiting embodiment, the diagnostic test device 900 uses a heating block 902 to apply heat to the amplification fluid in the diagnostic test storage 204 to perform an amplification reaction. The diagnostic test device 900 also guides an optical signal to the diagnostic test storage 204, and receives an optical signal from the diagnostic test storage 204 to detect the analyte of interest (if present) in the amplification fluid in the diagnostic test storage 204. The diagnostic test device 900 can use one or more image sensors (not shown) to optically scan a portion of the test container 112, such as the bottom portion 436 of the test container 112. This scanning can be used to detect and / or measure a positive control report in the amplification fluid. The measurement of the positive control report can confirm that the distribution action and the amplification reaction can proceed as expected. This scanning can also be used to detect and / or measure the process of the test determination reaction. For example, the diagnostic test device 900 can optically scan the bottom portion of the diagnostic test storage 204 to detect and / or measure the fluorescence change indicating the amplification reaction being carried out due to the presence of the analyte. As described above, the embodiments of the present disclosure are not limited to real-time detection during the reaction process, and in some cases, detection is performed when the reaction is completed.

[0192] Fig. 9A cross-sectional view of a diagnostic test device 100 housed in one or more heat blocks 902, 904 of a diagnostic test device 900 is illustrated. The diagnostic test device 100 includes a dispensing mechanism 102 housed in a sample preparation reservoir 202. In this non-limiting example, a test container 112 is received in a first heat block 902 of the diagnostic test device 900, and the sample preparation reservoir 202 is received in a second heat block 904 of the diagnostic test device 900. The second heat block 904 can apply heat to the cartridge body 108 to facilitate preparation of a sample for an assay or reaction in a fluid in the sample preparation reservoir of the cartridge body 108. The fluid contained within the sample preparation reservoir 202 can be heated as the cartridge body 108 is heated. After dispensing a subvolume of fluid in the sample preparation reservoir 202 into the test container 112, the heat block 902 can apply heat to the test container 112 to perform an amplification reaction in an amplification fluid present in the test container 112. Windows within the heat block 902 (not shown in this cross-sectional view) can allow optical signals to be directed to and received from one or more diagnostic test reservoirs 204 to detect analytes of interest in the amplification fluid, if present.

[0193] One or more optical sensors included in the diagnostic test device 900 can capture fluorescent signals emitted from the amplification fluid during or after the amplification reaction. The digital output from the one or more image sensors can be used to confirm the test assay progress and confirm the correct release and flow of test reagents within the cartridge so that the controller can confirm the integrity of the test and the integrity of the test is used to improve the reliability and accuracy of the test results.

[0194] Figure 10-18 The perspective view, front view, rear view, left side view, right side view, top view, bottom view, top exploded view and bottom exploded view of the diagnostic test device 100 including the cartridge body 108, the test container 112 and the dispensing cap 114 are illustrated respectively. Figures 3A-3C , 3F-3H and 4H, the test container 112 includes a capillary groove 304.

[0195] Manual operation, visual readout, non-instrument operation of diagnostic test devices

[0196] In some applications, the diagnostic test device 100 can be used manually without an instrument. For example, in some embodiments, the diagnostic test device 100 is held by one hand, while the other hand removes the transport cap 116, adds the sample, inserts the dispensing mechanism 102 into the barrel body 108, and the dispensing cap 114 is assembled to the barrel body 108 and rotated closed. In some such embodiments, where the (one or more) diagnostic test storages 204 are visually transparent, the distribution of the fluid into the (one or more) diagnostic test storages 204 can be visually observed, and the color or turbidity changes are observed over time to provide a diagnostic test reading or display. The method takes advantage of operating with a completely sealed barrel 106 once the sample is added and dispensing the measured volume of the prepared sample fluid internally into the (one or more) diagnostic test storages 204 without using an external fluid transfer step.

[0197] Optionally, a stand may be provided to support the diagnostic test device 100 for purposes of removing the shipping cap 116 , adding a sample, inserting the dispensing mechanism 102 , and fitting, closing, and locking the dispensing cap 114 to the cartridge body 108 .

[0198] Alternatively, a heat block may be provided to provide temperature control of the sample preparation reservoir 202 and diagnostic test reservoir(s) 204 of the diagnostic test device 100, but the diagnostic test device 100 is manually withdrawn to observe the test results visible in the diagnostic test reservoir(s) 204. In some applications, the heat block may include a window that allows visibility of the diagnostic test reservoir(s) 204. In such applications, the diagnostic test device 100 need not be removed from the heat block to observe the test results.

[0199] the term

[0200] Features referred to herein as “capillary grooves” may also be referred to as “capillary channels” and / or “capillary notches.” As a non-limiting example, a groove may be a long, narrow cut or depression, particularly a cut or depression used to guide motion.

[0201] Conjunctive language, such as the phrase "at least one of X, Y, and Z," is understood in context, unless expressly stated otherwise, to be generally used to convey that an item, term, etc., may be X, Y, or Z. Thus, such conjunction language is generally not intended to imply that certain embodiments require the presence of at least one of X, at least one of Y, and at least one of Z.

[0202] Language of degree as used herein, such as the terms "approximately," "about," "generally," and "substantially" as used herein, refers to a value, amount, or characteristic that approaches the stated value, amount, or characteristic that consistently performs a desired function or achieves a desired result. For example, the terms "approximately," "about," "generally," and "substantially" may refer to an amount that is less than within 10%, less than within 5%, less than within 1%, less than within 0.1%, and less than 0.01% of a specified amount.

[0203] As used herein, the term "and / or" has its broadest least restrictive meaning, i.e., the disclosure includes A alone, B alone, A and B together, or A or B, but does not require both A and B or require either A or B. As used herein, the phrase "at least one of" A, B, and C should be construed to mean a logical A or B or C, using a non-exclusive logical or.

[0204] Conditional language used herein, such as "may", "could", "might", "would", etc., unless otherwise expressly stated or otherwise understood in the context of use, is generally intended to convey that certain features, elements and / or steps are optional. Therefore, such conditional language is generally not intended to imply that features, elements and / or steps are required in any way. The terms "comprises", "comprising", "having", etc. are used inclusively in an open-ended manner and do not exclude additional elements, features, actions, operations, etc. In addition, the term "or" is used in its inclusiveness (rather than exclusivity) so that, for example, when used to connect a list of elements, the term "or" represents one, some or all of the elements in the list.

[0205] Any method disclosed herein need not be performed in the order described.The methods disclosed herein include certain actions taken by a practitioner; however, they may also include any third-party instructions for these actions, whether explicit or implicit.

[0206] Some or all of the methods and tasks described herein may be performed and fully automated by a computer system. A diagnostic test system according to the present disclosure may include a computer system, which in some cases may include a plurality of different computers or computing devices (e.g., physical servers, workstations, storage arrays, cloud computing resources, etc.), which may communicate and interoperate over a network to perform the functions described. Each such computing device typically includes a processor (or multiple processors) that executes program instructions or modules stored in a memory or other non-transient computer-readable storage medium or device (e.g., a solid-state storage device, a disk drive, etc.). The various functions disclosed herein may be embodied in such program instructions, and / or may be implemented in a dedicated circuit (e.g., an ASIC or FPGA) of a computer system. In the case where a computer system includes a plurality of computing devices, these devices may, but need not, be located in the same location. The results of the disclosed methods and tasks may be persistently stored by converting physical storage devices such as solid-state memory chips and / or disks into different states. The computer system may be a cloud-based computing system whose processing resources are shared by a plurality of different business entities or other users.

[0207] Although the above detailed description has shown, described and pointed out novel features, it is understood that various omissions, substitutions and modifications can be made in the described forms and details of the devices, systems and methods without departing from the spirit of the present disclosure. It can be appreciated that some parts described herein may be embodied in a form that does not provide all the features and benefits set forth herein, because some features can be used or practiced separately from other features. Therefore, the utility model is not limited to the specific embodiments disclosed herein, but covers all modifications and alternatives that fall within the true scope and spirit of the utility model.

Claims

1. A diagnostic test device, characterized in that include: a cartridge body, the cartridge body comprising a sample preparation reservoir; as well as A diagnostic test reservoir coupled to the cartridge body, the diagnostic test reservoir comprising at least one chamber, a plurality of spaced-apart valleys along an interior surface of the at least one chamber, the at least one chamber being configured to receive fluid from the sample preparation reservoir at a first section of the at least one chamber, each of the plurality of spaced-apart valleys comprising a curved cross-section and configured to facilitate flow of the fluid toward a second section of the at least one chamber.

2. The diagnostic test unit of claim 1, wherein the curved cross-section comprises a smooth arc.

3. The diagnostic test unit of claim 1 or 2, wherein each of the plurality of spaced-apart valleys comprises three inflection points.

4. The diagnostic test unit of any one of claims 1 to 3, wherein each of the plurality of spaced-apart valleys comprises three curved portions.

5. The diagnostic test unit of any one of claims 1 to 4, wherein each of the plurality of spaced apart valleys comprises two convex portions separated by a concave portion.

6. The diagnostic test unit of claim 1 or 2, wherein a transition between the interior surface of the at least one chamber and the plurality of spaced-apart valleys comprises a rounded edge.

7. The diagnostic test unit of any one of claims 1 to 6, wherein a valley of the plurality of spaced-apart valleys comprises a semi-circular or semi-elliptical cross-sectional shape.

8. The diagnostic test unit of any one of claims 1 to 7, wherein the plurality of spaced apart valleys are separated by planar portions of the interior surface of the at least one chamber.

9. The diagnostic test unit of any one of claims 1 to 8, wherein a portion of the interior surface in the second section of the at least one chamber forms a continuous circumferential surface.

10. The diagnostic test unit of any one of claims 1 to 9, wherein a portion of the interior surface in the second section of the at least one chamber forms a continuously curved surface.

11. The diagnostic test unit of any one of claims 1 to 10, wherein the inner surface forms a closed perimeter in the at least one chamber.

12. The diagnostic test unit of any one of claims 1 to 11, wherein a portion of the interior surface terminates in a smooth arc in the second section of the at least one chamber.

13. The diagnostic test device of claim 12, wherein a portion of the interior surface is continuous between the smooth arc in the first section of the at least one chamber and the second section of the at least one chamber.

14. The diagnostic test unit of any one of claims 1 to 13, wherein the at least one chamber further comprises a window region below ends of the plurality of spaced apart valleys.

15. The diagnostic test unit of any one of claims 1 to 13, wherein the at least one chamber further comprises a window region that does not include a valley of the plurality of spaced-apart valleys.

16. The diagnostic test unit of any one of claims 1 to 15, wherein a valley of the plurality of spaced-apart valleys tapers along a portion of its height. 17 . The diagnostic test device of claim 16 , wherein a valley of the plurality of spaced-apart valleys tapers beginning at a height between the first segment and the second segment.

18. The diagnostic test unit of any one of claims 1 to 17, wherein ends of valleys of the plurality of spaced apart valleys have a semi-circular profile.

19. The diagnostic test unit of any one of claims 1 to 18, wherein ends of valleys of the plurality of spaced-apart valleys have a tapered profile.

20. The diagnostic test device of any one of claims 1 to 19, wherein a first valley of the plurality of spaced-apart valleys extends a first distance toward the second section of the at least one chamber, and a second valley of the plurality of spaced-apart valleys extends a second distance toward the second section of the at least one chamber, the second distance being longer than the first distance.

21. The diagnostic test device of any one of claims 1 to 20, wherein a valley of the plurality of spaced-apart valleys has a cross-sectional shape in the first section of the at least one chamber that is different than a cross-sectional shape at an end of the valley.

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