Diagnostic test device with capillary grooves

Abstract

A diagnostic test device for performing tests on biological or environmental samples is provided. In one aspect, the diagnostic test device includes a chamber configured to receive fluid from a sample preparation reservoir in a first section of the chamber and one or more capillary grooves along an interior surface of the chamber. The capillary grooves are configured to facilitate fluid flow toward a second section of the chamber. Some embodiments of the diagnostic test reservoir can increase the amount of sample available for an assay reaction. In one embodiment, the assay reaction occurs within the volume of fluid in the second section of the chamber.

Description

[Technical Field]

[0001] [CROSS-REFERENCE TO RELATED APPLICATIONS] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 486,931, filed February 24, 2023, which is incorporated by reference in its entirety.

[0002] [Technical field] The present disclosure relates to optimizing the transport of sample solutions within consumables for diagnostic testing, particularly nucleic acid diagnostic testing. More specifically, the present disclosure relates to devices and methods for optimizing the amount of sample solution transferred from a sample preparation reservoir into a portion of a diagnostic test reservoir configured to receive thermal and light energy for the detection of an analyte in the sample solution. [Background technology]

[0003] Nucleic acid amplification is important in many fields, including medical, biomedical, environmental, veterinary, and food safety testing. Exemplary methods of nucleic acid amplification include polymerase chain reaction (PCR) amplification and isothermal amplification.

[0004] Nucleic acid amplification can generate multiple copies of a target genetic sequence in a test solution. Specific markers can be designed to link to the target sequence as part of a test assay. Once bound, the marker can provide a detectable signal (e.g., an optical signal) from the test solution. The change in the optical signal can include a change in color, opacity, bioluminescence, and / or fluorescence of the test solution. In the case of fluorescent marker beacons, each marker molecule can be configured with a fluorescence quencher in close proximity to a fluorescent atom or atomic sequence. The marker molecule can be configured such that, upon selective binding to the target nucleic acid sequence, the quencher and fluorophore are separated, allowing a fluorescent signal to be detected by the action of the fluorophore. In such a configuration, the fluorescence intensity of the target solution indicates the relative amount of target genetic material in the test solution. This signal can then be used to form the basis of a diagnostic test to determine the presence or relative amount of a target substance or analyte in the sample being tested.

[0005] A single test well can contain two or more markers, each providing a light 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 combination with these two or more markers. For example, in a two-channel system, two different fluorophores can be used that can be detected by two different fluorescent sensors configured to detect the emission of each fluorophore in its respective frequency range. Thus, two channels can be distinguished.

[0006] Such an approach can be used to provide a control channel. In an exemplary control channel, the test assay chemistry is configured so that a control target (e.g., a synthetic nucleic acid sequence) is always present if the test process is running correctly. The output of the control channel can be used to confirm that the test process is running correctly by the system and / or to validate test results obtained by other channels measured by the system. This approach can be applied to testing multiple target sequences in a single test well.

[0007] Multiple test wells can be used, each carrying a different amplification chemistry and / or a different set of target markers. As previously mentioned, control channels can be activated in one or more wells.

[0008] Consumable diagnostic test devices may be implemented that implement multiple test wells. The consumable diagnostic test devices may be disposable, single-use devices targeted at the point-of-care market (where ease of use, simplicity, and cost per consumable are important considerations). The consumables may be formed from polypropylene, a plastic that is easily molded to form mass-produced parts with high chemical resistance and is readily available at a relatively low cost. Polypropylene has relatively low water vapor permeability, facilitating long-term storage of dry reagents within polypropylene consumables. Nucleic acid-based diagnostic tests typically require an elution lysis buffer (ELB) to elute test specimens from sample collection devices, such as swabs, and release genomic material from the test specimen for molecular diagnostic testing. ELBs are often aqueous solutions. As a result, the highly polar nature of ELBs may interact with the relatively low polarity of polypropylene in consumable diagnostic test devices, potentially impairing test performance. For example, droplets of ELB may adhere to the polypropylene surface due to the poor wettability of polypropylene. This can reduce the amount of ELB available for testing. As another example, droplets of ELB that adhere to the walls early in the reaction can subsequently fall to the bottom of the reaction chamber, altering the concentrations of reactants (including, but not limited to, analytes and reagents) and causing a detectable change in output. Thus, there is a need for improvement in many aspects of consumable-type diagnostic tests, particularly nucleic acid-based diagnostic tests that use aqueous solutions to extract and test nucleic acids of interest. Summary of the Invention

[0009] In one non-limiting embodiment, a diagnostic testing device is provided. The diagnostic testing device includes a cartridge body containing a sample preparation reservoir and a diagnostic testing reservoir coupled to the cartridge body. The diagnostic testing reservoir has at least one chamber and one or more capillary grooves along an interior surface of the at least one chamber configured to receive fluid from the sample preparation reservoir in a first section of the at least one chamber. The one or more capillary grooves are configured to facilitate flow of the fluid toward a second section of the at least one chamber.

[0010] The one or more capillary grooves may be configured to inhibit droplets of the fluid from adhering to the interior surface of the first section of the at least one chamber when the fluid is dispensed from the sample preparation reservoir into the at least one chamber, and the one or more capillary grooves may be configured to increase the volume of the fluid collected in the second section of the at least one chamber.

[0011] The at least one chamber may be configured to transmit a fluorescent signal. The flow of the fluid may be downward from the first section to the second section. The second section may have a closed end.

[0012] The diagnostic testing device may include a seal between the sample preparation reservoir and the at least one chamber, the seal configured to prevent movement of the fluid between the sample preparation reservoir and the at least one chamber, and a dispensing mechanism configured to break the seal to allow movement of the fluid from the sample preparation reservoir into the at least one chamber.

[0013] The diagnostic test device may include the fluid, which may include an aqueous buffer, which may include at least one of RBCC, GRBS, and SDS.

[0014] The sample preparation reservoir may be configured to receive a test sample. The sample preparation reservoir may be configured to receive a swab containing the test sample. At least a portion of the fluid and at least a portion of the test sample may be configured to move from the sample preparation reservoir to the at least one chamber.

[0015] The at least one chamber may include two diagnostic test reservoirs, each of which may include one or more capillary channels. The at least one chamber may include plastic. The plastic may include polypropylene. The at least one chamber may be coupled to the cartridge body via ultrasonic welding.

[0016] The one or more capillary grooves can be configured to facilitate movement of the fluid into contact with a lyophilized reagent in the second section of the at least one chamber, the lyophilized reagent can include nucleic acid amplification primers and nucleic acid amplification detection probes.

[0017] The one or more capillary grooves may have a plurality of spaced apart valleys along the interior surface of the at least one chamber, and each of the plurality of spaced apart valleys may have a curved cross-section, and the curved cross-section may include a smooth arc.

[0018] Each of the plurality of spaced valleys may have three inflection points. Each of the plurality of spaced valleys may have three curvatures. Each of the plurality of spaced valleys may have two convex portions separated by a concave portion. A transition between the inner surface of the at least one chamber and the plurality of spaced valleys may have rounded edges. One of the plurality of spaced valleys may have a semicircular or semi-elliptical cross-sectional shape. The plurality of spaced valleys may be separated by a flat portion of the inner surface of the at least one chamber.

[0019] A portion of the inner surface of the second section of the at least one chamber may form a continuous circumferential surface. A portion of the inner surface of the second section of the at least one chamber may form a continuous curved surface. The inner surface may form a closed periphery within the at least one chamber. A portion of the inner surface may terminate in a smooth arc within 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 within the second section of the at least one chamber.

[0020] The at least one chamber may include a window region below an end of the spaced valleys. The at least one chamber may include a window region that does not include any of the spaced valleys.

[0021] One of the plurality of spaced valleys may be tapered along a portion of its height. The one of the plurality of spaced valleys may begin to taper at a height between the first section and the second section. An end of the one of the plurality of spaced valleys may have a semicircular contour. An end of the one of the plurality of spaced valleys may have a tapered contour.

[0022] A first valley of the plurality of spaced 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 valleys may extend a second distance toward the second section of the at least one chamber, the second distance being greater than the first distance. One valley of the plurality of spaced valleys may have a cross-sectional shape at the first section of the at least one chamber that is different from the cross-sectional shape at an end of the valley.

[0023] In another non-limiting embodiment, a method for performing a diagnostic test using a diagnostic testing device is provided. The diagnostic testing device includes a sample preparation reservoir and a diagnostic test reservoir. The method includes dispensing fluid from the sample preparation reservoir into at least one chamber of the diagnostic test reservoir. One or more capillary grooves are provided along an interior surface of the at least one chamber, the one or more capillary grooves being 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 further includes detecting the presence or absence of an analyte in the at least one chamber.

[0024] The method may further comprise adding a test sample to the fluid in the sample preparation reservoir prior to dispensing the fluid into the at least one chamber. The method may further comprise rehydrating lyophilized reagents in the at least one chamber using the fluid dispensed from the sample preparation reservoir. Performing the amplification reaction may comprise applying heat to the at least one chamber. Detecting the presence or absence of the analyte may comprise detecting a change in fluorescence emission indicative of a test result, the fluorescence emission exiting the at least one chamber through a portion of a wall of the at least one chamber, the portion of the wall not including a capillary groove. Dispensing the fluid may comprise collecting the fluid in the section of the at least one chamber, the one or more capillary grooves may be configured to increase the volume of the fluid collected in the section of the at least one chamber. The method may further comprise flowing the fluid along the one or more capillary grooves toward the section of the at least one chamber.

[0025] The one or more capillary grooves may have a plurality of spaced apart valleys along the inner surface of the at least one chamber, and each of the plurality of spaced apart valleys may have a curved cross-section.

[0026] The curved cross-section may include a smooth arc. Each of the plurality of spaced valleys may have three inflection points. Each of the plurality of spaced valleys may have three curvatures. Each of the plurality of spaced valleys may have two protrusions separated by a recess.

[0027] A transition between the interior surface of the at least one chamber and the plurality of spaced valleys may have rounded edges. One of the plurality of spaced valleys may have a semicircular or semi-elliptical cross-sectional shape. The plurality of spaced valleys may be separated by flat portions of the interior surface of the at least one chamber.

[0028] The embodiments provided herein include the following numbered embodiments: 1. A cartridge body containing a sample preparation reservoir; a diagnostic test reservoir coupled to the cartridge body and having at least one chamber and one or more capillary grooves along an interior surface of the at least one chamber; Equipped with the at least one chamber configured to receive fluid from the sample preparation reservoir in a first section of the at least one chamber; The one or more capillary grooves are configured to facilitate flow of the fluid toward a second section of the at least one chamber. 1. A diagnostic test device comprising: 2. The one or more capillary grooves are configured to inhibit droplets of the fluid from adhering to the interior surface of the first section of the at least one chamber when the fluid is dispensed from the sample preparation reservoir into the at least one chamber. 2. The diagnostic test device of embodiment 1. 3. The one or more capillary grooves are configured to increase the volume of the fluid collected in the second section of the at least one chamber. 3. A diagnostic test device as recited in claim 1 or 2. 4. The at least one chamber is configured to transmit a fluorescent signal. 4. A diagnostic test device according to any one of embodiments 1 to 3. 5. The flow of the fluid is downward from the first section to the second section. 5. A diagnostic test device according to any one of embodiments 1 to 4. 6. The second section has a closed end. 6. A diagnostic test device according to any one of embodiments 1 to 5. 7. A seal between the sample preparation reservoir and the at least one chamber. Further provided with The seal is configured to prevent transfer of the fluid between the sample preparation reservoir and the at least one chamber. 7. A diagnostic test device according to any one of embodiments 1 to 6. 8. A dispensing mechanism configured to break the seal and allow movement of the fluid from the sample preparation reservoir into the at least one chamber. 8. The diagnostic test device of embodiment 7, further comprising: 9. The diagnostic test device includes the fluid; The fluid comprises an aqueous buffer solution. 9. A diagnostic test device according to any one of embodiments 1 to 8. 10. The aqueous buffer solution contains at least one of RBCC, GRBS, and SDS. 10. The diagnostic test device of embodiment 9. 11. The sample preparation reservoir is configured to receive a test sample. 10. The diagnostic test device of embodiment 9. 12. The sample preparation reservoir is configured to receive a swab containing the test sample; At least a portion of the fluid and at least a portion of the test sample are configured to move from the sample preparation reservoir to the at least one chamber. 12. The diagnostic test device of claim 11. 13. The at least one chamber includes two diagnostic test reservoirs; each of said diagnostic test reservoirs containing one or more capillary grooves; 13. A diagnostic test device according to any preceding embodiment. 14. The at least one chamber comprises plastic. 14. A diagnostic test device according to any preceding embodiment. 15. The plastic includes polypropylene. 15. The diagnostic test device of embodiment 14. 16. The at least one chamber is coupled to the cartridge body via ultrasonic welding. 16. The diagnostic test device of embodiment 14 or 15. 17. The one or more capillary grooves are configured to facilitate movement of the fluid in contact with the lyophilized reagent in the second section of the at least one chamber. 17. A diagnostic test device according to any preceding embodiment. 18. The freeze-dried reagent contains a nucleic acid amplification primer and a nucleic acid amplification detection probe. 18. The diagnostic test device of embodiment 17. 19. The one or more capillary grooves have a plurality of spaced valleys along the interior surface of the at least one chamber; Each of the plurality of spaced valleys has a curved cross section. 19. A diagnostic test device as recited in any preceding embodiment. 20. The curved cross section includes a smooth arc. 20. The diagnostic test device of embodiment 19. 21. Each of the plurality of spaced valleys has three inflection points. 21. The diagnostic test device of embodiment 19 or 20. 22. Each of the plurality of spaced valleys has three curvatures. 22. A diagnostic test device according to any one of embodiments 19 to 21. 23. Each of the plurality of spaced valleys has two protrusions separated by a recess. 23. A diagnostic test device as recited in any one of embodiments 19 to 22. 24. A transition between the inner surface of the at least one chamber and the plurality of spaced valleys has rounded edges. 21. The diagnostic test device of embodiment 19 or 20. 25. One of the plurality of spaced valleys has a semicircular or semi-elliptical cross-sectional shape. 25. A diagnostic test device according to any one of embodiments 19 to 24. 26. The plurality of spaced valleys are separated by flat portions of the interior surface of the at least one chamber. 26. A diagnostic test device according to any one of embodiments 19 to 25. 27. A portion of the inner surface of the second section of the at least one chamber forms a continuous circumferential surface. 27. A diagnostic test device according to any one of embodiments 19 to 26. 28. A portion of the inner surface of the second section of the at least one chamber forms a continuous curved surface. 28. A diagnostic test device according to any one of embodiments 19 to 27. 29. The inner surface forms a closed periphery within the at least one chamber. 29. A diagnostic test device according to any one of embodiments 19 to 28. 30. A portion of the inner surface terminates in a smooth arc within the second section of the at least one chamber. 30. A diagnostic test device as recited in any one of embodiments 19-29. 31. A portion of the inner surface is 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. 31. The diagnostic test device of embodiment 30. 32. The at least one chamber further includes a window area below the ends of the plurality of spaced valleys. 32. A diagnostic test device as recited in any one of embodiments 19 to 31. 33. The at least one chamber further includes a window region that does not include any of the plurality of spaced valleys. 32. A diagnostic test device as recited in any one of embodiments 19 to 31. 34. One of the plurality of spaced valleys is tapered along a portion of its height. 34. A diagnostic test device according to any one of embodiments 19 to 33. 35. The one valley of the plurality of spaced valleys begins to taper at a height between the first section and the second section. 35. The diagnostic test device of embodiment 34. 36. An end of one of the plurality of spaced valleys has a semicircular profile. 35. A diagnostic test device according to any one of embodiments 19 to 34. 37. An end of one of the plurality of spaced valleys has a tapered profile. 36. A diagnostic test device according to any one of embodiments 19 to 35. 38. A first valley of the plurality of spaced valleys extends a first distance toward the second section of the at least one chamber; a second valley of the plurality of spaced valleys extending a second distance toward the second section of the at least one chamber; The second distance is greater than the first distance. 38. A diagnostic test device as recited in any one of embodiments 19-37. 39. One of the plurality of spaced valleys has 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. 39. The diagnostic test device of any one of embodiments 19-38. 40. A method of performing a diagnostic test using a diagnostic test device, comprising: the diagnostic testing device includes a sample preparation reservoir and a diagnostic testing reservoir; The method comprises: dispensing fluid from the sample preparation reservoir into at least one chamber of the diagnostic test reservoir; conducting an amplification reaction in said at least one chamber; detecting the presence or absence of an analyte in said at least one chamber; Equipped with one or more capillary grooves along an interior surface of the at least one chamber; The one or more capillary grooves are configured to facilitate flow of the fluid toward a section of the at least one chamber. A method characterized by: 41. Adding a test sample to the fluid in the sample preparation reservoir prior to distributing the fluid into the at least one chamber. 41. The method of embodiment 40, further comprising: 42. Rehydrating the lyophilized reagent in the at least one chamber with the fluid dispensed from the sample preparation reservoir. 42. The method of embodiment 40 or 41, further comprising: 43. The step of carrying out the amplification reaction includes applying heat to the at least one chamber. 43. The method according to any one of embodiments 40 to 42. 44. The step of detecting the presence or absence of the analyte comprises detecting a change in fluorescence emission indicative of a test result; the fluorescent emission exits the at least one chamber through a portion of a wall of the chamber; The portion of the wall does not include a capillary groove. 44. The method according to any one of embodiments 40 to 43. 45. The step of distributing the fluid includes collecting the fluid within the section of the at least one chamber; the one or more capillary grooves are configured to increase the volume of the fluid collected within the section of the at least one chamber. 45. The method of any one of embodiments 40 to 44. 46. ​​Flowing the fluid along the one or more capillary channels toward the section of the at least one chamber. 46. ​​The method of any one of embodiments 40 to 45, further comprising: 47. The one or more capillary grooves have a plurality of spaced valleys along the interior surface of the at least one chamber; Each of the plurality of spaced valleys has a curved cross section. 47. The method according to any one of embodiments 40 to 46. 48. The curved cross section includes a smooth arc. 48. The method of embodiment 47. 49. Each of the plurality of spaced valleys has three inflection points. 49. The method of embodiment 47 or 48, 50. Each of the plurality of spaced valleys has three curvatures. 50. The method of any one of embodiments 47 to 49. 51. Each of the plurality of spaced valleys has two protrusions separated by a recess. 51. The method according to any one of embodiments 47 to 50. 52. A transition between the inner surface of the at least one chamber and the plurality of spaced valleys has rounded edges. 52. The method of embodiment 47 or 51, 53. One of the plurality of spaced valleys has a semicircular or semi-elliptical cross-sectional shape. 53. The method of any one of embodiments 47 to 52. 54. The plurality of spaced valleys are separated by flat portions of the interior surface of the at least one chamber. 54. The method of any one of embodiments 47 to 53.

[0029] The foregoing aspects, as well as other features, aspects, and advantages of embodiments of the present disclosure, will be described in connection with various implementations with reference to the accompanying drawings. The illustrated embodiments are by way of example only and are not intended to be limiting. Like reference numerals refer to like elements throughout the drawings, unless the context dictates otherwise. [Brief explanation of the drawings]

[0030] [Figure 1] FIG. 1 shows an exploded view of the components of an exemplary diagnostic testing device according to the present disclosure.

[0031] [Figure 2A] FIG. 2A shows the exemplary diagnostic test device of FIG. 1 with a dispensing cap.

[0032] [Figure 2B] FIG. 2B shows the exemplary diagnostic test device of FIG. 1 with a shipping cap.

[0033] [Figure 3A] 3A-3C show diagrams of the test vessel shown in FIGS. 1-2B. [Figure 3B]3A-3C show diagrams of the test vessel shown in FIGS. 1-2B. [Figure 3C] 3A-3C show diagrams of the test vessel shown in FIGS. 1-2B.

[0034] [Figure 3D] FIG. 3D illustrates the relationship between the radius of the capillary groove and the contact angle of a liquid, according to one embodiment of the present disclosure.

[0035] [Figure 3E] FIG. 3E shows a diagram of an exemplary test vessel that does not include a capillary groove.

[0036] [Figure 3F] 3F-3H show views of the test vessel shown in FIGS. 1-2B. [Figure 3G] 3F-3H show views of the test vessel shown in FIGS. 1-2B. [Figure 3H] 3F-3H show views of the test vessel shown in FIGS. 1-2B.

[0037] [Figure 3I] 3I and 3J show diagrams of an exemplary test vessel according to one embodiment of the present disclosure. [Figure 3J] 3I and 3J show diagrams of an exemplary test vessel according to one embodiment of the present disclosure.

[0038] [Figure 4A] FIG. 4A shows a view of the cartridge body of the embodiment shown in FIG.

[0039] [Figure 4B] FIG. 4B shows a view of the cylindrical chamber of the embodiment shown in FIG. 4A.

[0040] [Figure 4C] FIG. 4C shows a cross-sectional view of the cylindrical chamber of the embodiment shown in FIG. 4A.

[0041] [Figure 4D] 4D and 4E show cross-sectional views of the cartridge body of the embodiment shown in FIG. 4A. [Figure 4E] 4D and 4E show cross-sectional views of the cartridge body of the embodiment shown in FIG. 4A.

[0042] [Figure 4F] FIG. 4F shows a side view of the cartridge body of the embodiment shown in FIG. 4A.

[0043] [Figure 4G] FIG. 4G shows a top view of the cartridge body of the embodiment shown in FIG. 4A.

[0044] [Figure 4H] FIG. 4H shows an enlarged view of the test vessel of FIG.

[0045] [Figure 5A] FIG. 5A shows the dispensing cap of FIG.

[0046] [Figure 5B] FIG. 5B shows a cross-sectional view of another dispensing cap according to the present disclosure.

[0047] [Figure 5C] FIG. 5C shows a cross-sectional view of the dispensing cap of FIG. 5B engaged with the cartridge body of the embodiment of FIG.

[0048] [Figure 5D] FIG. 5D shows the interaction of the locking tab of the dispensing cap of FIG. 1 with the locking screw of the cartridge body of FIG.

[0049] [Figure 5E] FIG. 5E illustrates the interaction of the over-travel tab of the dispensing cap of FIG. 1 with the blocking flange of the cartridge body of FIG.

[0050] [Figure 6A]FIG. 6A shows a side view of the dispensing mechanism of FIG.

[0051] [Figure 6B] FIG. 6B shows an oblique bottom view of the dispensing mechanism of FIG.

[0052] [Figure 6C] 6C and 6D show alternative embodiments of seal members according to the present disclosure. [Figure 6D] 6C and 6D show alternative embodiments of seal members according to the present disclosure.

[0053] [Figure 6E] 6E and 6F are top and bottom views, respectively, of an alternative embodiment of the seal member shown in FIGS. 6C and 6D. [Figure 6F] 6E and 6F are top and bottom views, respectively, of an alternative embodiment of the seal member shown in FIGS. 6C and 6D.

[0054] [Figure 7A] FIG. 7A shows a cross-sectional view of the embodiment of FIG. 1 with the dispensing mechanism inserted into the sample preparation reservoir.

[0055] [Figure 7B] FIG. 7B shows a cross-sectional view of the embodiment of FIG. 1 with the dispensing mechanism penetrating the seal.

[0056] [Figure 7C] FIG. 7C shows a cross-sectional view of the embodiment of FIG. 1, with the seal member engaging the wall of the cylindrical chamber but not penetrating the seal.

[0057] [Figure 7D] Figures 7D and 7E show cross-sectional views of the embodiment of Figure 1 with the dispensing mechanism fully inserted to dispense a predetermined amount of fluid into the diagnostic test reservoir. Figure 7D shows the piercing member in more detail than Figure 7E. Figure 7E shows the entire diagnostic test device. [Figure 7E] Figures 7D and 7E show cross-sectional views of the embodiment of Figure 1 with the dispensing mechanism fully inserted to dispense a predetermined amount of fluid into the diagnostic test reservoir. Figure 7D shows the piercing member in more detail than Figure 7E. Figure 7E shows the entire diagnostic test device.

[0058] [Figure 8] 1 illustrates an exemplary method for performing a diagnostic test using a diagnostic test device according to the present disclosure.

[0059] [Figure 9] 2 shows the diagnostic test device of FIG. 1 housed in a portion of a diagnostic test machine.

[0060] [Figure 10] 10-18 show diagrams of exemplary diagnostic test devices according to the present disclosure. [Figure 11] 10-18 show diagrams of exemplary diagnostic test devices according to the present disclosure. [Figure 12] 10-18 show diagrams of exemplary diagnostic test devices according to the present disclosure. [Figure 13] 10-18 show diagrams of exemplary diagnostic test devices according to the present disclosure. [Figure 14] 10-18 show diagrams of exemplary diagnostic test devices according to the present disclosure. [Figure 15] 10-18 show diagrams of exemplary diagnostic test devices according to the present disclosure. [Figure 16] 10-18 show diagrams of exemplary diagnostic test devices according to the present disclosure. [Figure 17] 10-18 show diagrams of exemplary diagnostic test devices according to the present disclosure. [Figure 18] 10-18 show diagrams of exemplary diagnostic test devices according to the present disclosure.

[0061] [Figure 19A] 19A-19C show examples of clouding or droplet formation in a device that does not include capillary grooves according to the present disclosure. [Figure 19B] 19A-19C show examples of clouding or droplet formation in a device that does not include capillary grooves according to the present disclosure. [Figure 19C] 19A-19C show examples of clouding or droplet formation in a device that does not include capillary grooves according to the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0062] Embodiments of the present disclosure provide devices, systems, and methods that can optimize the transfer of a solution (e.g., a sample solution) from one portion of a diagnostic testing device to another portion of the device. The solution may include a highly polar liquid, such as a water-based solution, which tends to be retained on surfaces formed of less polar materials, such as plastic surfaces, when the solution contacts or otherwise interacts with the surface. The surface may include, for example, the surface of a component formed of polypropylene, across or along which the solution can pass as it is transferred within the diagnostic testing device. Embodiments of the present disclosure include surfaces having one or more capillary grooves. The capillary grooves may be shaped and sized to promote solution flow, e.g., downward flow. For example, embodiments of diagnostic testing devices including capillary grooves according to the present disclosure may advantageously reduce the tendency of the solution to form droplets on the surface during transfer from one portion of the diagnostic testing device to another portion of the device.

[0063] Reducing or eliminating variable, uncontrolled, and / or inefficient solution transfer using capillary groove embodiments according to the present disclosure may increase the volume of solution received within the portion of a diagnostic testing device where a test is performed, thereby increasing the amount of sample available for an assay reaction. For example, embodiments of the present disclosure may advantageously increase the volume of solution transferred from a sample preparation reservoir to a test reservoir (or portion of a test reservoir) within a diagnostic testing device, where heat and / or light energy is delivered to perform a diagnostic test. Advantageously, increasing the volume of solution reliably and consistently delivered to a test reservoir using embodiments of the present disclosure may increase the amount of analyte included in an assay or other test reaction, contributing to diagnostic test results with greater accuracy and specificity. Furthermore, using embodiments of the present disclosure to increase the volume of solution reliably and consistently delivered to a test reservoir can ensure that a reagent (e.g., a dried reagent) in the test reservoir is reconstituted to a target concentration. For example, embodiments of the present disclosure can allow an assay to be designed and / or optimized based on the reliable and consistent delivery of a desired amount of solution to the region of the test reservoir where the reagent is reconstituted.

[0064] The elution lysis buffer (ELB) used in diagnostic testing platforms is often an aqueous solution. Consumables used in diagnostic testing (e.g., but not limited to, cartridges, tubing, reaction chambers) are often made of or contain plastics such as polypropylene or polyethylene. Commonly packaged plastics, such as polypropylene and polyethylene, are relatively low-polarity materials. As a result, the high polarity characteristic of ELBs can cause beading on the surfaces of plastic components of consumables, such as reaction chambers, that are configured to receive solutions.

[0065] This interaction can result in a less-than-optimal amount of solution available for testing on the diagnostic testing platform. For example, the ELB containing the collected patient sample may bead up and / or develop a cloudy appearance on the relatively non-polar plastic (polypropylene in this non-limiting example) on the inner surface of the reaction chamber wall. Figures 19A-19C illustrate this phenomenon. For example, test reservoir 1902 may include two reaction chambers 1910, each including an inner surface 1912. While a portion of the ELB solution 1906 may diffuse to the bottom of reaction chamber 1910, another portion of the ELB solution may remain at the top of inner surface 1912 in the form of droplets 1908 and cloud 1904. In these instances, the volume of ELB solution 1906 at the bottom of reaction chamber 1910 is reduced because some of the ELB containing the collected patient sample is present in droplets 1908 or cloud 1904 rather than in the volume of ELB solution 106 at the bottom of reaction chamber 1910. In some cases, droplet 1908 may not participate in the reaction occurring at the bottom of test reservoir 1902. In some cases, droplet 1908 may adhere to the wall of reaction chamber 1910, only to fall to the bottom of test reservoir 1902 where the reaction is occurring, changing the concentration of reagents in ELB solution 1906 as the reaction proceeds.

[0066] 19A, the volume of ELB solution 1906 at the bottom of reaction chamber 1910 is reduced because the diffused ELB is present in droplets 1908 and cloudiness 1904. ELB can diffuse from the top of reaction chamber 1910 and fall or flow to the bottom of chamber 1910. However, in many cases, some of the ELB remains on top of surface 1912 of chamber 1910 and exists as cloudiness 1904 and droplets 1908 as shown. The volume (amount) of ELB solution 106 at the bottom of each chamber 1910 is unequal due to the unequal degree of droplet formation and cloudiness between the two chambers 1910.

[0067] In Figure 19B, a portion of the volume of ELB solution dispensed into reaction chamber 1910 is present in the form of droplets 1908. The amount of ELB solution 106 reduced at the bottom of chamber 1910 is related to the volume (amount) of droplets 1908. In Figure 19B, the ELB solution 1906 at the bottom of each chamber 1910 is unequal because the droplets are not of the same volume (amount). As shown, droplets 1908 on surface 1912 of left chamber 1910 are larger than droplets 1908 on surface 1912 of right chamber 1910; therefore, the volume of ELB solution 1906 at the bottom of left chamber 1910 is smaller than the volume of ELB solution 1906 at the bottom of right chamber 1910.

[0068] In FIG. 19C , a portion of the ELB solution dispensed into reaction chamber 1910 resides in droplets 108 formed at the top corners of reaction chamber 1910, thereby reducing the volume of ELB solution 1906 at the bottom of reaction chamber 1910. ELB solution may be dispensed from the top of reaction chamber 1910 and may fall or flow to the bottom of chamber 1910. However, as shown in FIG. 19C , the dispensed ELB solution often collects at the top corners. The geometry of the top corners of reaction chamber 1910 provides two surfaces to which droplets 1908 may adhere. The formation of droplets 1908 also reduces the volume of ELB solution 1906 present at the bottom of chamber 1910.

[0069] Beading and / or clouding of the ELB solution can result in variability in the amount of sample-containing ELB solution introduced to the bottom of the reaction chamber, where reagents for the assay reaction may reside. Beading and / or clouding can also result in unintended variability in the amount of collected test specimen available for the assay reaction. This can lead to inaccuracies in assay results because the amount (e.g., volume) of test specimen available for the assay reaction is not well controlled. Furthermore, beading and / or clouding can introduce variability in the concentration of reagents reconstituted within the reaction chamber, leading to inconsistent or inaccurate assay results. These variability issues can be particularly severe when test specimens are delivered from one reservoir to another (e.g., reaction chamber 1910) and the ELB solution is exposed to a surface made of plastic (e.g., inner surface 1912 of reaction chamber 1910).

[0070] In some cases, the sample present in the ELB solution may contain genomic material. Beading and / or clouding of the ELB solution may affect, for example, the amount of available genomic material (e.g., DNA or RNA) introduced into an amplification reaction. For example, beading and / or clouding of the ELB solution may reduce the amount of genomic material present at a location within reaction chamber 1910, such as the bottom of reaction chamber 1910, where the amplification reaction occurs.

[0071] As mentioned above, in addition to reducing sample variability, a consistent ELB dispense volume may be desirable to ensure that the lyophilized reagent in the reaction chamber is reconstituted to a target concentration. As an example, beading and / or cloudiness may reduce the amount of ELB solution ultimately delivered to the target location in the diagnostic test platform, resulting in the lyophilized reagent being reconstituted at a higher than intended concentration. As a result, assays using these lyophilized reagents may not perform as intended (e.g., the assay may produce inaccurate or inconsistent results).

[0072] Embodiments of the present disclosure provide devices, systems, and methods that can ensure a more consistent ELB diffusion volume by minimizing or eliminating ELB beading on the inner surface of a target reservoir, such as a reaction chamber. For example, embodiments of the present disclosure provide for capillary grooves within the reaction chamber, which can promote droplet flow to the bottom of the reaction chamber. In embodiments in which 100 μL of sample-containing fluid is diffused into a diagnostic test reservoir, the capillary grooves can prevent 20-30 μL of sample-containing fluid from floating on the walls of the diagnostic test reservoir. In other words, in these embodiments, the capillary grooves increase the volume available for the assay reaction by 20-30 μL.

[0073] Embodiments of the present disclosure provide devices, systems, and methods that can consistently transfer a predetermined volume of a solution, such as a fluid sample, from one portion of a diagnostic testing device to another portion of the device while avoiding contamination of the solution and the external environment. The fluid sample may include a test sample in a buffer solution. In some cases, the liquid sample is ready for amplification when transferred from a first portion to a second portion. The first portion of the diagnostic testing device may include a sample preparation reservoir, and the second portion of the diagnostic testing device may include one or more test vessels. For example, a predetermined volume of the fluid sample may be transferred from the sample preparation reservoir to one or more test vessels containing pre-stored amplification reagents. The one or more test vessels may include a surface having capillary grooves shaped and sized to promote flow (e.g., downward flow) of the fluid sample into a portion of the one or more test vessels. For example, the capillary grooves may facilitate movement of the fluid sample to a portion of one or more test vessels to which heat and / or light energy is delivered to perform a diagnostic test. The sample processing device can include dual internal cylinders through which a predetermined volume of fluid sample can be dispensed into two test vessels using a plunger. Advantageously, both test vessels can include surfaces having capillary grooves, thereby reliably and consistently delivering a predetermined volume of solution to predetermined portions of both test vessels where an assay or test reaction is performed. Prior to transfer of the fluid sample, the test vessels are sealed from the external environment and the sample preparation reservoir to protect them from contaminants. After transfer of the liquid sample, the test vessels remain sealed from the external environment. Advantageously, the external environment is not exposed to the fluid sample, which may contain hazardous components.

[0074] The diagnostic testing device of the present disclosure can dispense a predetermined amount of fluid sample simultaneously with sealing the sample receiving end of the sample preparation reservoir. For example, twisting a cap engaged with the sample receiving end of the sample preparation reservoir dispenses the fluid sample from the sample preparation reservoir into a test vessel. When dispensing the liquid sample, the cap can lock, preventing access to the sample preparation reservoir and test vessel and protecting them from contamination. Additional fluid flow between the sample preparation reservoir and the test vessel is also prevented. The mechanism for dispensing a fluid sample while simultaneously sealing the diagnostic testing device is not complex and involves the movement of only a single component within the sample processing reservoir. In particular, the dispensing mechanism includes a plunger configured to directly contact the inner surface of the sample processing reservoir as the plunger moves within the sample preparation reservoir, with a piercing end of the plunger piercing one or more seals separating the sample preparation reservoir and the test vessel. After being dispensed, the fluid sample in the test vessel can be assayed using, for example, 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 amounts of a fluid sample from a single sample preparation reservoir into two or more test vessels containing different reagents, allowing for multiple testing of a single sample.

[0075] Embodiments of the present disclosure provide devices, systems, and methods by which a test sample can be prepared and then tested, for example, by amplification in combination with a fluorescent marker. One embodiment includes a diagnostic test assembly (also referred to herein as a "cartridge") for use with a diagnostic testing instrument to perform diagnostic tests on biological or environmental samples. Such a cartridge can be used with a diagnostic testing machine (also referred to herein as an "instrument"). As described herein, the cartridge is easy for a user to operate without requiring typical laboratory equipment.

[0076] Throughout the following description, various embodiments are described with reference to an exemplary implementation of a rapid nucleic acid-based diagnostic system capable of testing for a variety of diseases. By way of example, the system may test for sexually transmitted infections (STIs) such as gonorrhea and chlamydia, and respiratory infections (RTIs) such as influenza A or influenza B. This exemplary system is targeted to the point-of-care (POC) market, where ease of use, simplicity, CLIA waiver, and fast turnaround time (TAT) for results are considered. However, it will be understood that any of the devices, systems, and methods described herein may be applied to any other medical, forensic, or other applications.

[0077] The present disclosure relates to devices, systems, and methods capable of performing amplification (e.g., isothermal amplification) of nucleic acids in a sample. Unless otherwise specified, when the term amplification is used herein, it is intended to encompass all variations of amplification, including, but not limited to, isothermal amplification and PCR amplification (including real-time PCR and quantitative PCR). It will be understood that the devices, systems, and methods of the present disclosure are not limited to amplifying nucleic acids, but may test a sample for the presence or absence of any target of interest. It will also be understood that the devices, systems, and methods of the present disclosure are not limited to processing or conditioning a sample before the sample is tested for the presence or absence of a target of interest.

[0078] [Example of diagnostic test equipment] 1-7E, an exemplary diagnostic test instrument 100 according to the present disclosure will now be described.

[0079] The diagnostic testing device 100 is implemented in a rapid, nucleic acid-based testing system capable of performing automated molecular diagnostic tests for detecting various analytes. The diagnostic testing device 100 includes a cartridge 106 configured to be inserted into the diagnostic instrument of the testing system. In one non-limiting example, the cartridge 106 is a disposable plastic container. The cartridge 106 may be formed of injection-molded plastic or any other suitable material. The cartridge 106 may include a barcode, such as a barcode displayed on the exterior surface of the cartridge 106. The barcode may be scanned by the diagnostic testing device to automatically identify the assays to be performed on the patient sample added to the cartridge 106. In this non-limiting example, the assays include a sample preparation assay and an isothermal amplification assay for detecting a nucleic acid of interest. A user may enter patient and / or sample information via the instrument's touchscreen or barcode scanning.

[0080] In addition to a cartridge 106, the diagnostic testing instrument 100 includes a dispensing mechanism 102 configured to interface with the cartridge 106, as shown in FIG. 1. The cartridge 106 includes a cartridge body 108, a test container 112, and one or more seals 110a, 110b. The diagnostic testing instrument 100 may include a closure configured to close a first end 120 of the cartridge body 108. For example, the diagnostic testing instrument 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, for example, O-rings, gaskets, grommets, etc. In the non-limiting embodiment of FIG. 1, the one or more sealing members 104 include two O-rings. As shown in FIGS. 2A and 2B , the dispense cap 114 and the transport cap 116 are each configured to attach to and close or seal the first end 120 of the cartridge body 108. In one example, the transport cap 116 is configured to reversibly close or seal the first end 120, and the dispense cap 114 is configured to irreversibly close or seal the first end 120. The cartridge body 108 includes a sample preparation reservoir 202 and one or more cylindrical chambers 206. The cartridge body 108 may form the sample preparation reservoir 102 and one or more cylindrical chambers 206. A substance, such as a fluid, present in the sample preparation reservoir 202 and the one or more cylindrical chambers 206 may be enclosed within the cartridge 108. The test vessel 112 includes one or more diagnostic test reservoirs 204. Test vessel 112 may form one or more diagnostic test reservoirs 204. A substance, such as a fluid, present in one or more diagnostic test reservoirs 204 may be enclosed within test vessel 112.

[0081] The test vessels 112 of the cartridge 106 may take any suitable shape and size. In the non-limiting embodiment of Figures 1-7, the test vessels 112 include one or more tubes, each tube forming a single diagnostic test reservoir 204. However, it will be understood that other configurations may be suitably implemented.

[0082] Embodiments of diagnostic testing devices, systems, and methods according to the present disclosure may include a test vessel 112 that minimizes or eliminates sample-containing fluid retention, e.g., by droplet formation, on the walls of the test vessel 112 where no assay or test reaction occurs. For example, thermal and / or optical signals associated with assay reactions, such as nucleic acid amplification and detection, may be directed toward the bottom of the diagnostic test reservoir 204 but not toward the top of the diagnostic test reservoir 204. Thus, sample-containing fluid present as droplets or a cloud at the top of the diagnostic test reservoir 204 may not receive heat as intended. Similarly, sample-containing fluid present as droplets or a cloud may not be properly positioned to receive and emit optical signals (or other signals used to detect assay results). Furthermore, by ensuring that sample-containing fluid dispensed into the diagnostic test reservoir 204 is consistently and reliably dispersed to the bottom of the diagnostic test reservoir 204, variability in assay results can be reduced. Consistent and reliable diffusion of sample-containing fluid to the bottom of the diagnostic test reservoir 204 may also ensure a higher likelihood that sufficient sample material, e.g., genomic material, will be available for an assay reaction to ensure accurate test results. Accordingly, embodiments of the diagnostic test device, diagnostic test system, and diagnostic test method disclosed herein may advantageously increase the amount of sample available for an assay reaction, which, in one embodiment, occurs within the volume of fluid received and / or collected at the bottom of the test vessel 112. By reducing the formation of droplets on the walls or interior surfaces of the test vessel 112, embodiments of the diagnostic test device, diagnostic test system, and diagnostic test method disclosed herein may prevent and / or reduce the likelihood that droplets of fluid will adhere to the walls or interior surfaces of the test vessel 112 prior to a reaction and then fall to the bottom of the reaction chamber while the reaction is in progress.

[0083] Figures 3A, 3B, and 3H show cross sections of test vessel 112. Figure 3F shows a top plan view of test vessel 112. Figure 3G shows a bottom view of test vessel 112. Figure 4H also shows a view of test vessel 112. One end 312 of test vessel 112 is open and configured to receive fluid, allowing it to pass into one or more diagnostic test reservoirs 204. The other end 314 of test vessel 112 is a closed end. End 314 may be the bottom closed end of one or more diagnostic test reservoirs 204. End 314 is configured to collect fluid.

[0084] Amplification of analytes of interest may occur in diagnostic test reservoirs 204 of test vessels 112. Cartridge body 108 may be coupled to diagnostic test reservoirs 204, and isothermal amplification and fluorescent detection may occur in diagnostic test reservoirs 204. When attached to cartridge body 106 using seals 110a and / or 110b, one or more diagnostic test reservoirs 204 are physically and fluidly isolated from one another. A second end 118 of cartridge body 108 opposite first end 120 may be coupled to one end 312 of test vessel 112. Other configurations may also be suitably implemented. For example, in another non-limiting embodiment, cartridge body 108 and test vessel 112 are integrated into a single structure. Amplification (e.g., but not limited to, isothermal amplification) and detection (e.g., but not limited to, fluorescent detection) of one or more analytes of interest may occur in one or more diagnostic test reservoirs 204. Optical signals may be directed toward one or more diagnostic test reservoirs 204, and optical signals emitted from one or more diagnostic test reservoirs 204 may be detected and correlated with the presence, absence, and possibly quantity, of one or more analytes of interest. The walls of the test vessel 112 may comprise a plastic, such as polycarbonate and / or polypropylene, or any other suitable material (e.g., but not limited to, polyethylene). It may be desirable to select a material that is transparent, substantially transparent, and / or non-opaque to facilitate transmission of the optical signal through the walls of the test vessel 112. The test vessel 112 may also include a lip 302 to facilitate attachment of the test vessel 112 to the cartridge body 108, as disclosed herein. The test vessel 112 may include one or more protrusions 310 located on or around the lip 302.

[0085] The present disclosure is not limited to test vessels 112 having two diagnostic test reservoirs 204 as shown in Figures 1, 3A-3C, 3E-3H, and 4H. For example, test vessels 112 may also be implemented with one diagnostic test reservoir 204. Alternatively, test vessels 112 may be implemented with three, four, or more diagnostic test reservoirs 204.

[0086] The test vessel 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 along at least a portion of the height of the interior surface of the diagnostic test reservoir 204. In some embodiments, no portion of the capillary groove protrudes into the interior space of the test vessel 112. Because each capillary groove 304 may be an indentation in the interior wall of the diagnostic test reservoir 204, a test vessel 112 having one or more capillary grooves 304 may have a larger interior volume than a test vessel 112 without capillary grooves. Figure 3E shows an embodiment of a test vessel 112b having a diagnostic test reservoir 204b that does not include capillary grooves.

[0087] As shown in FIG. 3C , when viewed from above, the cross section of each capillary groove 304 may be semicircular and / or semi-elliptical. It will be understood that capillary grooves 304 having other cross-sectional profiles may also be suitably implemented in embodiments of the present disclosure. As shown in FIGS. 3A , 3B , and 3H , a portion of the capillary groove 304 may terminate substantially above the end 314 of the test vessel 112 and above the window region 308. The window region(s) 308 have substantially planar and / or flat walls, resulting in no, substantially no, or minimal optical interference due to the geometry of the walls of the test vessel 112. The window region(s) 308 do not include the capillary groove 304. Optical detection of an analyte of interest may involve transmission of an excitation signal and / or a detection signal through the window region(s) 308. In some embodiments, the blunt ends of the blunt-ended capillary groove(s) 318 may define the tops of the window region(s) 308. The window area is located near the end 314 of the test vessel 112 and is located away from the end 312 of the test vessel 112. In another embodiment, none of the capillary grooves 304 extend to the end 314 of the test vessel 112. In yet another embodiment, all of the capillary grooves 304 extend to the end 314 of the test vessel 112.

[0088] It may be advantageous for some of the capillary grooves 304 to extend all the way to or near the end 314 to facilitate fluid flow across the entire height of the diagnostic test reservoir 204. In some embodiments, the overall length of the capillary grooves 304 (e.g., the total distance the capillary grooves 304 extend from end 312 toward end 314) may depend in part on the total amount (volume) of liquid to be dispensed into the diagnostic test reservoir 204. In facilitating the flow of fluid droplets toward end 314, it may be desirable for the capillary grooves 304 to be able to carry these fluid droplets up to at least the top surface of the fluid already located at end 314. Thus, as an illustrative example, if the volume of liquid dispensed into the diagnostic test reservoir 204 is substantially greater than half the total volume of the diagnostic test reservoir 204, the capillary groove 304 need not extend below approximately half the height of the diagnostic test reservoir 204, since the top surface of the dispensed liquid will be above the lower end of the capillary groove 304. In the embodiment illustrated in Figures 3A, 3B, and 3H, if 100 μl of fluid were to be dispensed into each of the diagnostic test reservoirs 204, the top surface of the fluid would be higher than the top surface of the window area 308. Thus, even a shorter, blunt-ended capillary groove 318 would extend through the surface of the fluid. In some embodiments, one or more capillary grooves, such as tapered capillary groove 316, may be tapered as they approach the end 314 of the test vessel. In some embodiments, one or more capillary grooves, such as blunt capillary groove 318, are not tapered but instead have a rounded blunt end 320 as they approach end 314. In some embodiments, at least one of the capillary grooves is tapered capillary groove 316 and at least one of the capillary grooves is blunt capillary groove 318. In one non-limiting example, near end 312 of test vessel 112, blunt capillary groove 318 may have a width of about 0.5 mm. Near the blunt end, blunt capillary groove 318 may remain about 0.5 mm wide (e.g., not tapered). Blunt capillary groove 318 may extend about 14 mm from the top of diagnostic test reservoir 204 to the top of window area 308. In embodiments in which the test vessel 112 is manufactured by injection molding, it may be desirable to tape the capillary groove 304 to allow or assist in pulling the test vessel 112 from the core of the injection mold.

[0089] In some embodiments, a "tapered" capillary groove narrows and / or decreases in width as the capillary groove approaches the end 314. For example, as indicated 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 vessel 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 may be approximately 0.5 mm near the end 312 of the test vessel 112. In some embodiments, the width W may be approximately 0.3 mm, and the width w may be even smaller. The depth d of the tapered capillary groove 316 may also decrease as the tapered capillary groove 314 approaches the end 314. For example, near the end 312 of the test vessel 112, the depth d of the tapered capillary groove may be about 0.25 mm, which may correspond to an arc length a of the capillary groove of about 0.64 mm. In some embodiments, the tapered capillary groove 316 is not tapered throughout its entire length, but begins to taper at a height below the end 312. The tapered capillary groove 316 may include a taper over a distance L. In some embodiments, the tapered capillary groove 316 may begin to taper above the blunt end of the blunt capillary groove 318. In some embodiments, the tapered capillary groove 316 begins to taper near the height of the blunt end of the blunt capillary groove 318. In some embodiments, the tapered capillary groove 316 may extend closer to the end 314 of the test vessel 112 than the blunt capillary groove 318. Tapered capillary groove 316 may continue to end 314 of test reservoir 204 or may terminate above end 314 of test reservoir 204 .

[0090] 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 may be dimensioned to optimize the flow of liquid by capillary action or wicking. The optimal dimensions of a capillary configured to facilitate liquid flow depend in part on the properties of the liquid itself. Equation 1 expresses the relationship of various parameters for the flow of droplets down a capillary groove. JPEG2026506983000002.jpg9170Here, h is the liquid altitude, T is the surface tension of the fluid, θ is the contact angle (radian) between the liquid and the capillary groove, p is the liquid density, and g is the standard gravitational acceleration (9.8 m / s 2 ), and r is the radius of the capillary groove. The relationship between the liquid contact angle θ (in degrees) and the radius r of the capillary groove (while other variables are held constant) is plotted in Figure 3D. In Figure 3D, the height h was set to 15 mm, which is approximately equal to the length between the edge 312 of the test vessel 112 and the window area 308. In Figure 3D, the surface tension T was assumed to be that of water at room temperature (0.072 dyne / m), and the density p was assumed to be the density of water at room temperature (997.77 kg / m 3 ) was assumed. Assuming a particular height h and a fluid with properties similar to water at room temperature, the radius r and / or contact angle θ can be selected for a particular application. In other words, the capillary groove parameters that are optimal for a particular use case can be advantageously selected. For example, the contact angle θ for a particular application a is optimal, the radius r aA capillary groove having a radius r of 0.25 mm may be selected. In some embodiments of the test vessel 112, which have a capillary groove height of 15 mm and are intended for use with fluids having properties similar to room-temperature water, the radius of the capillary groove is 0.25 mm, corresponding to a liquid contact angle θ of approximately 76 degrees. Figure 3D shows the case of a 0.25 mm capillary groove radius and a 76° contact angle with dashed lines. A 0.25 mm capillary groove radius is suitable for use with room-temperature water because it is not so small as to be difficult to manufacture and provides a relatively high contact angle. A high contact angle may better promote capillary action of a droplet than a low contact angle. The aforementioned parameters, such as the radius r of the capillary groove, may be optimized to promote the flow of other liquids having properties different from water (e.g., different viscosities, surface tensions, and / or densities). Furthermore, the number of capillary grooves included may be selected to optimize fluid flow toward the end 314 of the diagnostic test reservoir 204. In general, providing additional capillaries may further promote fluid flow toward end 314, while reducing the number of capillaries may reduce fluid flow toward end 314 and / or preserve wall area of ​​test vessel 112 for transmission of signals, such as optical signals.

[0091] The test container 112 may include a detection tab 306. The detection tab 306 may facilitate detection of the presence or absence of the test container 112 contained within the diagnostic tester. For example, the diagnostic tester may include a sensor (e.g., a mechanical sensor) configured to interact with the detection tab 306 of the test container 112. When the test container 112 is inserted into the diagnostic tester, the detection tab 306 may press against the mechanical sensor of the diagnostic tester, indicating that the test container 112 is properly seated within the diagnostic tester. Other configurations may also be suitably implemented. For example, the diagnostic tester may include an optical sensor that emits an optical signal that is blocked by the detection tab 306 when the test container 112 is properly seated. The detection tab 306 may include a "stepped" shape, as shown in FIG. 4H. Additionally, the test container 112 may include a lip 430 to facilitate attachment of the test container 112 to the cartridge body 108, as described in more detail below.

[0092] One or more diagnostic test reservoirs 204 may be pre-loaded with reaction components for performing a particular diagnostic test. For example, one or more diagnostic test reservoirs 204 may contain lyophilized reagents. The lyophilized reagents may include enzymes, primers, probes, beacons, salts, and / or other reagents used in an assay reaction. One or more diagnostic test reservoirs 204 may also contain mixing beads. The beads may be magnetic beads. The beads may be embedded within a pellet of lyophilized reagents. When a fluid sample is introduced into one or more diagnostic test reservoirs 204 and the lyophilized reagents are rehydrated, the beads may facilitate mixing of the lyophilized reagents with the fluid sample. For example, the beads may be moved within one or more diagnostic test reservoirs 204 under the influence of magnetic force, causing movement within the liquid within the one or more diagnostic test reservoirs 204 and assisting in dissolution of the lyophilized reagents. The beads may comprise stainless steel or any other suitable material. In alternative embodiments, one or more diagnostic test reservoirs 204 may be pre-loaded with liquid reagents. In such embodiments, it may be desirable to mix the pre-loaded liquid reagents with the fluid sample, for example, by agitating magnetic beads contained within one or more diagnostic test reservoirs 204. In some embodiments, one or more diagnostic test reservoirs 204 may include one or more fins 322. The fins 322 may provide a surface for the lyophilized reagents to grip, thereby promoting adhesion of the lyophilized reagents to the bottom of the diagnostic test reservoir 204.

[0093] A non-limiting example of a capillary groove according to the present disclosure will now be described with reference to Figures 3I and 3H. Figures 3I and 3H show plan and cross-sectional views of a test container 112 of a diagnostic test device. Features previously described with reference to Figures 3A-3C, 3F-3H, and 4H may also be implemented in this non-limiting example. Diagnostic test reservoir 204 includes a chamber 324 configured to receive fluid from a sample preparation reservoir in a first section 326 of chamber 324. In this example, the capillary groove includes a plurality of spaced valleys 328 along the inner surface of chamber 324. The plurality of spaced valleys 328 are configured to promote fluid flow toward a second section 330 of chamber 324. The plurality of spaced valleys 328 may be configured to inhibit droplets of fluid from adhering to the inner surface of first section 326 of chamber 324 when fluid is dispensed from the sample preparation reservoir into chamber 324. The plurality of spaced valleys 328 may be configured to increase the volume of fluid collected in the second section 330 of the chamber 324 .

[0094] Each of the plurality of spaced valleys 328 has a curved cross-section. The curved cross-section may include a smooth arc a. A valley of the plurality of spaced valleys 328 may have three inflection points P. A valley of the plurality of spaced valleys 328 may have three curvatures C1, C2, and C3. A valley of the plurality of spaced valleys 328 may have two convex portions CV separated by a concave portion CC. A transition between the inner surface of the chamber 324 and the plurality of spaced valleys 328 may have a rounded edge 332. A valley of the plurality of spaced valleys 328 may have a semicircular or semi-elliptical cross-sectional shape. The plurality of spaced valleys 328 may be separated by a flat portion 334 on the inner surface of the chamber 324.

[0095] A portion of the inner surface of the second section 330 of the chamber 324 may form a continuous circumferential surface. A portion of the inner surface of the second section 330 of the chamber 324 may form a continuous curved surface. The inner surface may form a closed periphery within the chamber 324. A portion of the inner surface may terminate in a smooth arc 342 within the second section 330 of the chamber 324. A portion of the inner surface may be continuous between the first section 326 of the chamber 324 and the smooth arc of the second section 330 of the chamber 324.

[0096] The chamber 324 can include a window region 308 below the ends of the plurality of spaced valleys 328. The window region 308 does not include any of the plurality of spaced valleys 328.

[0097] One of the plurality of spaced valleys 328 may be tapered along a portion of its height. The valley may begin to taper at a height between the first section 326 and the second section 330. An end 336 of one of the plurality of spaced valleys 328 may have a semicircular profile 338. An end 336 of one of the plurality of spaced valleys 328 may have a tapered profile 340. A first valley of the plurality of spaced valleys 328 may extend a first distance toward the second section 330 of the chamber 324, and a second valley of the plurality of spaced valleys 328 may extend a second distance toward the second section 330 of the chamber 324, the second distance being greater than the first distance. A valley of the plurality of spaced valleys 328 may have a cross-sectional shape in the first section 326 of the chamber 324 that is different from the cross-sectional shape at the end of the valley.

[0098] 4A-4G illustrate aspects of a cartridge body 108 according to the present disclosure. As shown in the cross-sectional view of FIG. 4D, 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 illustrated in FIGS. 4A and 4D. The cartridge body 108 may also include a lower surface 424 of the cylindrical chambers 206. The sample preparation reservoir 202 may be pre-loaded with reaction components for performing a particular diagnostic test. For example, the sample preparation reservoir 202 may be pre-loaded with a volume of sample preparation fluid. A sample may be retained on a swab and inserted into the sample preparation reservoir 202. The sample preparation reservoir 202 may contain a sample preparation fluid, and the sample may be washed from the swab into the sample preparation fluid, thereby creating a fluid sample in the sample preparation reservoir 202. The fluid sample in the sample preparation reservoir 202 may be configured to undergo processing to collect and / or concentrate nucleic acids, such as DNA and / or RNA. In some embodiments, the sample preparation fluid may include an ELB. As illustrative examples, the ELB may include red blood cell lysis buffer (RBCC), glycine running buffer (GRBS), and / or sodium dodecyl sulfate solution (SDS). In alternative embodiments, the sample preparation fluid need not be pre-loaded into the sample preparation reservoir 202 but may be loaded immediately before the sample is introduced.

[0099] Figure 4B shows a cross-sectional top view of the second end 118 of the cartridge body 108 indicated by the dotted box in Figure 4A. Figure 4C shows a cross-sectional side view from dotted line 422 in Figure 4A.

[0100] The sample preparation reservoir 202 may have a fluid volume many times larger than the one or more diagnostic test reservoirs 204. As an example, the sample preparation reservoir 202 may have a volume of approximately 6 mL, and the one or more diagnostic test reservoirs 204 may accommodate a total fluid volume of approximately 400 pL. In some embodiments, the sample preparation reservoir 202 may hold a fluid volume of 0 to 5 mL, 0.5 to 4.5 mL, 1 to 4.0 mL, 1.5 to 3.5 mL, 2 to 3 mL, or any value within or bounded by any of these ranges or values. In some cases, values ​​outside these values ​​or ranges may also be used. Additionally or alternatively, in some embodiments, the sample preparation reservoir 202 may hold a fluid volume of 1 to 3 mL. The amount of sample preparation fluid actually held by the sample preparation reservoir 202 may depend on the particular assay.

[0101] The one or more diagnostic test reservoirs 204 are configured to receive a predetermined volume of fluid sample from the sample preparation reservoir 202 through a process according to the present disclosure (including, but not limited to, the exemplary process described below with reference to FIG. 8 ). The one or more diagnostic test reservoirs 204 may hold a fluid volume of 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 within or bounded by any of these ranges or numerical values. In some cases, values ​​outside of these numerical values ​​or ranges may also be used. Additionally or alternatively, in some embodiments, one or more diagnostic test reservoirs 204 may hold a fluid volume of 200 μL.

[0102] In some embodiments, the cartridge body 108 may include a geometry that facilitates rapid heating of the contents of the sample preparation reservoir 202. For example, the cartridge body 108 may have a relatively high surface area-to-volume ratio, such as by having an oval cross-section, to facilitate rapid heating. The walls of the cartridge body 108 may comprise a polypropylene material or any other suitable material (such as, but not limited to, polyethylene). In the embodiment shown in FIGS. 4A-4G, the cartridge body 108 transitions from a circular cross-section near the first end 120 to an oval cross-section lower within the cartridge body 108. As shown in FIGS. 4D, 4E, and 4G, the sloping wall 426 of the cartridge body 108 is a feature that transitions from a circular cross-section to an oval transverse cross-section. At the portion of the sloping wall 246 closest to the first end 120, the cross-section is relatively circular, and near the cylindrical chamber 206, the cross-section is relatively oval.

[0103] 5A and 5B, the dispensing cap 114 includes a locking tab 502, internal threads 504, an over-travel tab 506, a plug seal 508, and an inner ring 510 protruding from a flange 512. The inner ring 510 in this non-limiting embodiment 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 the end 606 of the dispensing mechanism 102 when the dispensing mechanism 102 is coupled to the dispensing cap 114. The inner ring 510 engages with a corresponding ring 610 on the end 606 of the dispensing mechanism 102, allowing the dispensing cap 114 to freely rotate around the dispensing mechanism 102 when the dispensing cap 114 is coupled to the end 606 of the dispensing mechanism 102. In an embodiment of the present disclosure, the dispensing mechanism 102 remains stationary after insertion into the cartridge body 108, while the dispensing cap 114 rotates about the longitudinal axis of the dispensing mechanism 102, as described in detail below.

[0104] In this non-limiting example, the inner ring 510 and ring 610 are reversibly coupled by a flexible interference fit, allowing the ring 610 to be reversibly snapped in and out of the inner ring 510. It will be appreciated that other mechanisms for coupling the dispensing cap 114 to the dispensing mechanism 102 may also be suitably implemented.

[0105] The threaded wall 404 on the first end 120 of the cartridge body 108 can be engaged by a cap (e.g., the dispense cap 114 or the shipping cap 116). In embodiments of the cartridge body 108 that include a locking screw 412, the locking screw 412 can also be engaged by a cap (e.g., the dispense cap 114). Twisting the locking tab 502 of the dispense cap 114 in a first direction (clockwise in this example) through the locking screw 412 locks the dispense cap 114 to the first end 120 of the cartridge body 108, thereby inhibiting and / or preventing movement of the dispense cap 114 in a second direction opposite the first direction (counterclockwise in this example). Figure 5D shows the locking tab 502 in a locked position, positioned relative to the locking screw 412. In the locked position, the dispense cap 114 is irreversibly engaged with the locking screw 412, preventing a user from unscrewing the dispense cap 114 or uncoupling the dispense cap 114 from the cartridge body 108. Advantageously, embodiments of the cartridge body 108 that include the locking screw 412 can completely seal the fluid sample within the device 100 when the dispense cap 114 is engaged with the locking screw 412. This can prevent contamination of the fluid sample 100 or leakage from the device 100 while or after a diagnostic test is being performed.

[0106] As shown in FIG. 5E , the blocking flange 428 of the cartridge body 108 can engage with the over-travel tab 506 of the dispensing cap 114. The blocking flange 428 can block the movement of the over-travel tab 506, thereby preventing or inhibiting further rotation of the dispensing cap 114 in a first direction (clockwise in this example). In some embodiments, engagement of the over-travel tab 506 with the blocking flange 428 occurs when the dispensing cap 114 is in substantially the same position as engagement of the locking screw 412 with the locking tab 502. That is, in some embodiments, the locking screw 412 and the blocking flange 428 engage with the locking tab 502 and the over-travel tab 506, respectively, such that the dispensing cap 114 cannot be twisted counterclockwise or clockwise after it is twisted into the locked position. When engaged, the blocking flange 428 and the over-travel tab 506 prevent rotational movement of the dispensing cap 114. When further rotational movement of the dispense cap 114 is prevented and / or inhibited, translational movement of the dispense cap 114 toward the end 410 of the cartridge body 108 is also prevented and / or inhibited. Advantageously, embodiments of the present disclosure allow translational movement of the dispense cap 114 toward the end 410 of the cartridge body 108 to be stopped at a very precise, predetermined distance from the end 410 of the cartridge body, thereby consistently dispensing a precise, predetermined volume of fluid from the sample preparation reservoir 202 into one or more diagnostic test reservoirs 204. In some non-limiting examples, rotating the dispense cap 114 another 7-10 degrees clockwise (past the locked position) dispenses an additional 10 μL of fluid from the sample preparation reservoir 202 into one or more diagnostic test reservoirs 204. In certain embodiments, dispensing an additional 10 μL is a 10% error in the dispensed volume. Thus, embodiments of the present disclosure that implement the blocking flange 428 and overtravel tab 506 may be able to consistently deliver precise amounts of fluid to one or more diagnostic test reservoirs 204, thereby improving the reliability and accuracy of the test.

[0107] In some embodiments of the present disclosure, the cartridge body 108 includes features strategically positioned to improve moldability and manufacturability of the cartridge body 108. In one non-limiting example, the protrusion of the cartridge body 108, including the locking screw 412 and the blocking flange 428, extends over less than half the circumference of the upper part of the cartridge body 108 (e.g., approximately 170° of the circumference). In some other embodiments, the protrusion may encompass a greater portion of the circumference of the upper part of the cartridge body 108 (e.g., 330° of the circumference) or a lesser portion of the circumference of the upper part of the cartridge body 108 (e.g., 45° of the circumference). In embodiments in which the cartridge body 108 is a single molded plastic part, a protrusion that encompasses less than 180° of the circumference of the cartridge body 108 may have better moldability because, in such non-limiting example, the protrusion on which the locking screw 412 and the blocking flange 428 are positioned does not intersect the parting line used during manufacturing (e.g., during the injection molding process).

[0108] 5B and 5C , the plug seal 508 of the dispense cap 114 is an annular flange extending from the top inner surface of the dispense cap 114. When in the locked position, the plug seal 508 can engage the first end 120 of the cartridge body 108. For example, as shown in FIG. 5C , the outer surface of the plug seal 508 can directly contact the inner surface of the first end 120 of the cartridge body 108. The plug seal 508 can prevent fluid within the cartridge body 108 from flowing or leaking out of the sample preparation reservoir 202 through the first end 120. Additionally, the plug seal 508 can prevent and / or inhibit fluid within the sample preparation reservoir from contacting the threaded wall 404 and / or threads 504. Thus, embodiments of the present disclosure implementing a dispense cap 114 with a plug seal 508 can advantageously reduce or eliminate the risk of contamination of the external environment by fluid within the sample preparation reservoir 202, which may contain pathogens.

[0109] In embodiments of the cartridge body 108 that include a key 402, the key 402 may engage a diagnostic test machine. The key 402 may help a user properly orient the cartridge 106 within the diagnostic test machine. Additionally or alternatively, the key 402 may be sensed by the diagnostic test machine to indicate insertion of the cartridge 106. Additionally or alternatively, in embodiments in which each diagnostic test reservoir 204 is loaded with a different reagent (e.g., lyophilized reagent), the key 402 may be used to orient the test container 112 to distinguish between each diagnostic test reservoir 204.

[0110] An 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, such as the cylindrical chamber 206. In the embodiment shown in FIGS. 4A-4G, the sides of the cylindrical chamber 206 are formed by the inner surface 420. While the cartridge body 108 in the illustrated embodiment includes two cylindrical chambers 206, other embodiments may include one or more cylindrical chambers 206. The cylindrical chambers 206 may include openings 418. Such openings facilitate the distribution of liquid from the sample preparation reservoir 202 to one or more diagnostic test reservoirs 204. The openings 418 may be covered by seals 110a. In certain embodiments, each opening 418 may be covered by its own seal 110a, and there may be one seal 110a for each opening 418.

[0111] It should be understood that the cartridge body 108 of the present disclosure is not limited to having two cylindrical chambers 206 as shown in Figures 1-3, 4A-4G, and 7A-7E. For example, the 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 reservoirs 206. The number of cylindrical chambers 206 in the cartridge body 108 may correspond to the number of diagnostic test reservoirs 204 in the test container 112.

[0112] Seals 110a, 110b may comprise a foil material and may be pierced by the application of mechanical force. Seals 110a, 110b need not be the same material, but in some embodiments may be. Seal 110b may be affixed to test vessel 112 and may cover an opening at first end 434 of test vessel 112, separating sample preparation reservoir 202 and one or more diagnostic test reservoirs 204. In one non-limiting embodiment, when cartridge body 108 and test vessel 112 are combined into a single cartridge 106, two seals 110a, 110b are pressed together. It may be desirable to attach seal 110b to the top of test vessel 112. For example, in certain embodiments in which test vessel 112 holds lyophilized reagents, attachment of seal 110b can ensure that moisture and / or other potential contaminants do not enter test vessel 112 before test vessel 112 and cartridge body 108 are joined. The presence of moisture and / or contaminants in test vessel 112 can result in inaccurate assay results, such as false positives or false negatives. When seal 110a is affixed to end 410 of one or more cylindrical chambers 206, it can retain fluid (e.g., liquid buffer) within sample preparation reservoir 202 and cylindrical chambers 206. As an illustrative example, seal 110a can be attached to the underside of cylindrical chamber 206 by heat sealing, and seal 110b can also be attached to the top of test vessel 112 via heat sealing.

[0113] In some embodiments, there may be only one of either seal 110. In such embodiments, the seal 110 may be installed over the opening 418 of the cylindrical chamber 206, or the seal 110 may be installed over the first end 434 of the test vessel 112 before the test vessel 112 and cartridge body 108 are coupled. In such embodiments, a single seal 110 may keep the fluid in the sample preparation reservoir 202 separate from one or more diagnostic test reservoirs. Similarly, a single seal 110 may keep the lyophilized reagents in the diagnostic test reservoir 204 separate from the sample preparation reservoir 202.

[0114] In the exemplary device 100, the cartridge body 108 is coupled to the test receptacle 112 during manufacturing and assembly of the device 100 prior to operation by an end user. Other embodiments may also be suitably implemented. 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 receptacle 112. In yet another non-limiting embodiment, the cartridge body 108 and test receptacle 112 are shipped separately to an end user, who couples the cartridge body 108 and test receptacle 112 prior to operation (i.e., before performing a test).

[0115] Cartridge body 108 can be connected to test vessel 112 using any number of coupling mechanisms, such as, but not limited to, lip 406 matingly connecting with lip 430 on the exterior surface of test vessel 112. Sample preparation reservoir 202 and one or more diagnostic test reservoirs 204 can be coupled via seals 110a and / or 110b therebetween to form cartridge 106. Thus, seal 110a can define the bottom of two cylindrical chambers formed by interior surface 420, while seal 110b can define the top of two diagnostic test reservoirs 204. Coupling (joining) sample preparation reservoir 202 and one or more diagnostic test reservoirs 204 via seals 110a therebetween to form a single coupled structure can be achieved, for example, by ultrasonic welding, adhesive, snap-fit ​​connections, combinations thereof, or any other suitable coupling mechanism. It may be desirable for the sample preparation reservoir 202 and the one or more diagnostic test reservoirs 204 to be coupled strongly enough to resist pressure buildup within the cylindrical chamber 206 and / or the one or more diagnostic test reservoirs 204. In embodiments in which the sample preparation reservoir 202 and the one or more diagnostic test reservoirs 204 are coupled via ultrasonic welding, the test vessel 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 to align the test vessel 112 with the end 410 and lip 406 at the second end 118 of the cartridge body 108 during ultrasonic welding. The one or more protrusions 310 may help to center the test vessel 112 with the lip 406 at the second end 118 of the cartridge body 108 during ultrasonic welding. For example, the one or more protrusions may ensure that the test vessel 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.

[0116] 5 illustrates a dispensing cap 114. The dispensing cap 114 may be coupled to a dispensing mechanism 102 according to embodiments of the present disclosure. The dispensing cap 114 may 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. The locking tab 502 may engage with the locking screw 412 of the cartridge body 108. Once the locking tab 502 of the dispensing cap 114 is rotated through the locking screw 412, further rotation in either direction may be prevented or inhibited, and the dispensing cap 114 may be locked to the cartridge body 108.

[0117] 6A and 6B illustrate aspects (features) of the dispensing mechanism 102. 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. Thus, there is a one-to-one correspondence between the piercing members 602, sealing members 104, cylindrical chambers 206, and diagnostic test reservoirs 204.

[0118] The shaft 604 and piercing member 602 of the dispensing mechanism 102 may comprise 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 spikes or other relatively sharp features sufficient to pierce a seal (such as, for example, seal 110a). In one example, the piercing member 602 comprises a spike rod. As shown in FIG. 6B, the profile and cross-section of the piercing member 602 may be cross- and / or plus-sign-shaped. The piercing member 602 may include a chamfered or beveled surface. For example, in the non-limiting embodiment of FIGS. 6A and 6B, a portion of each of the piercing members 602 includes a chamfered surface 614. The cross and / or plus sign shapes may facilitate fluid flow through the piercing member 602 and through the pierced seal 110a because fluid can flow more easily through the concave surface of the piercing member 602 while the chamfered surface 614 continues to enlarge the opening. Advantageously, the cross or plus sign shape of the piercing member 602 may form an opening in the seal 110a having a shape and size that facilitates fluid flow from the sample preparation reservoir 202 through the seal 110a. In one non-limiting example, the shape and size of the opening created in the seal 110a does not form lobes or sections of seal material that may obstruct or impede the passage of fluid through the opening.

[0119] Additionally, the cross or plus sign shape of the piercing member 602 may advantageously allow air to exit one or more diagnostic test reservoirs 204 and enter the sample preparation reservoir 202 before an opening is fully formed in the seal 110a. For example, air may move through the concave surface of the piercing member 602 while the chamfered surface 614 continues to enlarge the opening. Pressure buildup within one or more diagnostic test reservoirs 204, which would normally act to impede fluid flow into the one or more diagnostic test reservoirs 204, may be reduced as the opening is formed. This is particularly advantageous in scenarios where the air within one or more diagnostic test reservoirs 204 is pressurized. It will be appreciated that the aforementioned advantages of embodiments of the piercing member 602 are also applicable to the formation of an opening in the seal 110b.

[0120] It should be understood that the dispensing mechanism 102 of the present disclosure is not limited to (having) two piercing members 602 as shown in Figures 1 and 6A-7C. For example, the dispensing mechanism 102 may be implemented with one piercing member 602. Alternatively, the dispensing mechanism 102 may be implemented with three, four, or more piercing members 602. The number of piercing members 602 in the dispensing mechanism 102 may correspond to the number of cylindrical chambers 206 in the cartridge body 108.

[0121] The dispensing mechanism 102 may include one or more sealing members 104, such as, for example, an O-ring, a gasket, a grommet, or the like. The sealing member 104 may surround at least a portion of the piercing member 602. FIGS. 6A and 6B illustrate an embodiment in which the sealing member 104 is an O-ring. FIGS. 6C-6F illustrate an alternative embodiment in which the sealing member 104 is one or more gaskets. FIGS. 6E and 6F illustrate top and bottom views of alternative embodiments of the sealing member 104. In certain embodiments in which the sealing member 104 is a gasket, as shown in FIG. 6D, the sealing member may be formed separately from the dispensing mechanism 102 and coupled to the dispensing mechanism 102 by pressing the gasket sealing member 104 over the piercing member 602. In some embodiments, the gasket sealing member 104 may be overmolded over the piercing member 602 during the manufacturing process of the piercing member 602. 6C-6F, the gasket is a single piece of material forming two channels 610, each configured to receive one piercing member 602. The gasket also includes two annular portions 612 spaced a distance apart.

[0122] In one example in which the piercing member 602 includes a spiked rod, the seal member includes a seal member 104 that surrounds the spiked rod. The seal member 104 can be configured to directly contact the inner surface 420. In embodiments in which the seal 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 cartridge body 108. In some embodiments, such as the non-limiting example shown in FIGS. 6A and 6B , each O-ring includes two annular portions separated by a 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 cartridge body 108. In such cases, the presence of two independent annular portions can form a two-part seal against the inner surface 420 and can provide redundancy in case one annular portion does not form an effective seal against the inner surface. 6C-6F, substantially the entire circumference of each annular portion 612 may be in direct contact with the inner surface 420 of the cylindrical chamber 206 of the cartridge body 108. In such embodiments, the presence of two independent annular portions 612 separated by a distance may form a two-part seal against the inner surface 420 and may provide redundancy in the event that one annular portion 612 does not form an effective seal against the inner surface 420.

[0123] The seal member 104 may comprise an elastomeric material suitable for creating a liquid-tight or substantially liquid-tight seal when compressed against the material of the cartridge body 108. In some cases, the seal member 104 comprises a compressible material. In some non-limiting examples, the seal member 104 comprises rubber, butyl rubber, thermoplastic vulcanizate (TPV), and / or thermoplastic elastomer (TPE). In certain embodiments in which the seal member 104 is an O-ring, the seal member 104 comprises, for example, butyl rubber having a Shore A hardness of 70. In certain embodiments in which the seal member 104 is a gasket (either a gasket formed separately prior to coupling to the dispensing mechanism 102 or a gasket overmolded onto the dispensing mechanism), the seal member 104 may comprise TPV having a Shore A hardness of 60. It will be understood that many other materials may be suitably implemented in accordance with the present disclosure. The dispense cap 114 may be coupled to the dispensing mechanism 102. For example, the dispensing cap 114 can be coupled to the dispensing mechanism 102 such that it is rotatable about the longitudinal axis of the dispensing mechanism 102. In one non-limiting embodiment, the end 606 of the dispensing mechanism 102 engages with the inner ring 510 on the inner top surface of the dispensing cap 114 by a snap-fit ​​arrangement. This allows the dispensing mechanism 102 to rotate freely relative to the dispensing cap 114.

[0124] 4B and 4C, in embodiments having two or more cylindrical chambers 206, there may be an interior surface portion 414 separating two cylindrical chambers 206. The interior surface portion 414 between the two cylindrical chambers 206 may be formed to include a negative space, such as a notch 416. The notch 416 may define, at least in part, a predetermined volume of fluid dispensed from the sample preparation reservoir 202 to one or more diagnostic test reservoirs 204. Thus, the depth of the notch 416 may be varied to adjust the predetermined volume dispensed from the sample preparation reservoir 202 to one or more diagnostic test reservoirs 204.

[0125] The predetermined volume of fluid dispensed into one or more diagnostic test reservoirs 204 is defined by at least three variables: the radius of cylindrical chamber 206, the height H of cylindrical chamber 206 measured between lower surface 424 and the bottom of notch 416, and the volume displaced by piercing member 602. The depth of notch 416, shown as distance D in FIG. 4C , affects the height H at which one or more seal members 104 engage the inner surface between two cylindrical chambers 206 and is therefore inversely related to the predetermined volume dispensed. Three non-limiting examples are described below to illustrate the effect of notch 416 on the predetermined volume of fluid dispensed. For purposes of these three examples, the only dimensional change related to the predetermined volume of fluid dispensed is the depth D of notch 416.

[0126] 4B and 4C, the depth D of the notch 416 is approximately 0.2 mm, providing an embodiment in which approximately 100 μL of fluid is dispensed from each cylindrical chamber 206 into a corresponding diagnostic test reservoir 204. In a second non-limiting example, the depth D of the notch 416 is approximately 0.1 mm, providing an embodiment in which more than approximately 100 μL of fluid is dispensed from each cylindrical chamber 206 into a corresponding diagnostic test reservoir 204. This is because the depth D of the notch 416 in the second non-limiting example is smaller than the depth D of the notch 416 in the first example. In other words, in the second example, the one or more seal members 104 engage the inner surface between the two cylindrical chambers 206 at a height H that is greater than the height H in the first example, thereby enclosing a greater amount of fluid within the two cylindrical chambers 206. In a third non-limiting example, the depth D of the notch 416 is about 0.4 mm, dispensing a volume (amount) of fluid of less than about 100 μL into one or more diagnostic test reservoirs 204. This is because the depth D of the notch 416 in the third non-limiting example is greater than the depth D of the notch 416 in the first example. In other words, in the third example, the one or more seal members 104 engage the inner surface between the two cylindrical chambers 206 at a height H that is less than the height H of the first example, thereby enclosing a smaller amount of fluid within the two cylindrical chambers 206. In some embodiments, the depth D of the notch 416 is between about 0 mm and about 2 mm, between about 0 mm and about 1.5 mm, between about 0 mm and about 1 mm, or between about 0.1 mm and about 0.4 mm, although other values ​​or ranges may be used. In one non-limiting example of the present disclosure in which approximately 100 μL of fluid is dispensed into each diagnostic test reservoir 204, the depth D of the notch 416 is between about 0.1 mm and about 0.4 mm.

[0127] 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 open space within the dispensing mechanism 102. The slot 608 may allow one or more piercing members 602 and one or more seal members 104 to pass over a portion 414 of the inner surface between the two cylindrical chambers 206.

[0128] 7A-7E illustrate four different positions of the dispensing mechanism 102 within the sample preparation reservoir 202 during a dispensing operation in accordance with the present disclosure. This operation involves movement of the dispensing mechanism 102 relative to the cartridge body 108 to break seal 110a and / or seal 110b and force a predetermined amount of fluid into one or more diagnostic test reservoirs 204. Advantageously, embodiments of the presently disclosed devices, systems, and methods dispense a predetermined amount of fluid when one or more seal members come into direct contact with the interior surfaces defining the sides of the sample preparation reservoir 202 as the dispensing mechanism 102 moves along the longitudinal axis 108.

[0129] 7A shows the dispensing mechanism 102 inserted into the sample preparation reservoir 202 prior to engaging the threaded wall 404 with the dispensing cap 114. The dispensing mechanism 102 may be manually placed into this position by inserting it into the cartridge body 108 from above. The seals 110a, 110b are intact. As previously described, the dispensing mechanism 102 may be coupled to the dispensing cap 114. The dispensing cap 114 is configured to engage the threaded wall 404 of the sample preparation reservoir 202. The seal member 104 is positioned above the cylindrical chamber 206 and is not yet engaged therewith. On the other hand, because the sample preparation reservoir 202 is wider than it is deep (i.e., the cross section of the sample preparation reservoir when viewed from above is oval), the interior of the sample preparation reservoir 202 orients the dispensing mechanism 102 so that the piercing member 602 is substantially aligned with the cylindrical chamber 206 even when the piercing member 602 is positioned higher than the cylindrical chamber 206 within the cartridge body 108.

[0130] FIG. 7B shows the dispensing mechanism 102 after piercing seal 110a and / or seal 110b. Relative to the position shown in FIG. 7A, the dispensing mechanism 102 can assume the position shown in FIG. 7B after engaging the threaded wall 404 with the dispensing cap 114 and subsequently twisting the dispensing cap 114. As previously described, 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 freely rotate relative to the shaft 604 and piercing member 602. Thus, the interaction of the threaded wall 404 and the threads 504 translates twisting of the dispensing cap 114 into vertical translation of the dispensing mechanism 102 along the longitudinal axis 108. As the cap 114 is tightened relative to the cartridge body 108 with a clockwise twisting motion, the dispensing mechanism 102 moves downward. In this position, the dispensing cap 114 has not yet engaged the locking tab 502 and is still rotatable relative to the dispensing mechanism 102 and cartridge body 108 .

[0131] 7B, the dispensing mechanism 102 includes two seal 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 threaded onto the cartridge body 108 and further twisted, the dispensing mechanism 102 moves downward, causing the piercing members to approach and pierce the seals 110a, 110b. This movement forces the piercing member 602 to pass through the seal 110a.

[0132] As the dispensing mechanism 102 moves downward, air within the diagnostic test reservoirs 204 is compressed, so a pressure buildup may exist beneath the one or more seal members 104 within the one or more diagnostic test reservoirs 204. The threaded wall 404 and threads 504 may be configured to resist the upward force caused by this pressure buildup. When the dispensing cap 114 is locked by the locking screw 412, the interaction between the locking screw 412 and the dispensing cap 114 may also resist upward movement. Additionally, the bond between the test container 112 and the cartridge body 108 must also be strong enough not to fail due to this pressure buildup.

[0133] 7C shows the dispensing mechanism 102 and cartridge body 108 immediately after the piercing member 602 pierces the seal 110a and before fluid has flowed into one or more diagnostic test reservoirs 204. The seal members 104 engage the inner surface 420 of the cylindrical chamber 206. The lower surface of each seal member 104 has moved below the notch 416, causing each seal member 104 to create a complete seal with the inner surface 420 of the cylindrical chamber 206, preventing or substantially preventing fluid from flowing out of the seal member 104. That is, fluid cannot flow from below the seal member 104 to above the seal member 104, nor can fluid flow from above the seal member 104 to below the seal member 104. Because the lowest point of the notch 416 defines the height at which the top surface of the cylindrical chamber 206 can be defined, a predetermined volume is not defined until the lower surface of the seal member 104 passes directly below the notch 416. At the moment each piercing member 602 pierces seal 110a, a predetermined volume (shaded area) is defined by the inner surface 420 of cylindrical chamber 206, seal member 104, piercing member 602, and seal 110a. As dispensing mechanism 102 moves further downward, seal member 104 and piercing member 602 force the predetermined volume of fluid through the pierced seal 110a and into diagnostic test reservoir 204.

[0134] When a predetermined volume of fluid is forced through the perforated seal 110a, the capillary groove 304 of one or more diagnostic test reservoirs 204 is configured to facilitate the flow of the predetermined volume of fluid. The capillary groove 304 may facilitate flow from one end 312 of the test vessel 112 toward the other end 314 of the test vessel 112, resulting in the predetermined volume of fluid collecting at the window area 308. In some embodiments, the capillary groove 304 may facilitate a downward flow of the predetermined volume of fluid. The capillary groove 304 may prevent and / or inhibit clouding and / or droplets of the predetermined volume of fluid from adhering to the interior surface of the test vessel 112.

[0135] 7D and 7E, the entire dispensing mechanism 102 moves downward relative to the cartridge body 108 until the predetermined volume (of fluid), shown as the shaded area at the bottom of the diagnostic test reservoir 204 in FIG. 7E, is completely and / or substantially dispensed into the diagnostic test reservoir 204. In some embodiments, some amount of fluid may remain in the cylindrical chamber 206 when the dispensing cap 114 is locked. In some embodiments, once the predetermined volume (of fluid) is dispensed into the diagnostic test reservoir 204, the sealing member 104 may be flush with the lower surface 424 of the cylindrical chamber 206. In some embodiments, once the predetermined volume (of fluid) is dispensed into the diagnostic test reservoir 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 against the locking screw 412 and blocking flange 428 when the final portion of the predetermined volume (of fluid) is expelled from one or more cylindrical chambers 206. This inhibits and / or prevents rotation of the dispensing cap 114 relative to the cartridge body 108 and shaft 604, thereby preventing further and / or reverse translational movement of the dispensing mechanism 102 relative to the cartridge body 108. These and other features may allow embodiments of a diagnostic test reservoir 100 according to the present disclosure to precisely and consistently dispense a predetermined volume of fluid into a diagnostic test container.

[0136] With the piercing member 602 and the seal member 104 locked in place as described above, the predetermined volume of fluid to be dispensed into the one or more diagnostic test reservoirs 204 is contained within the test vessel 112. The piercing member 602 and the seal member 104 block the passage of the predetermined volume of fluid from the diagnostic test reservoirs 204. Furthermore, with the piercing member 602 and the seal member 104 locked in place, neither additional fluid nor other potential contaminants external to the diagnostic test device can enter the one or more diagnostic test reservoirs 204 or the sample preparation reservoir 202. As described below with respect to sample processing, the predetermined volume of fluid contained within the one or more diagnostic test reservoirs may be subjected to treatments, such as thermal and / or optical treatments. Such treatments may serve to generate results indicative of the presence or absence of one or more target analytes in a sample introduced into the diagnostic test device 100.

[0137] Sample processing using diagnostic testing equipment FIG. 8 illustrates an exemplary process 800 for using a diagnostic device 100 according to the present disclosure. The process may be performed using illustrated embodiments, such as those illustrated by FIGS. 1-7C and 9, as well as other embodiments according to the present disclosure. In use, the cartridge 106 is provided with a transport cap 116 that engages with a threaded wall 404 of the cartridge body 108. The transport cap 116 is removed from the cartridge body 108. For example, instructions for use of the device 100 may instruct the user to unscrew the transport cap 116 from the cartridge body 108. In block 802, a swab is inserted into the sample preparation reservoir 202 of the cartridge body 108 for sample deposition. The instructions may instruct the user to swirl the tip of the swab within the sample preparation reservoir 202 according to a predefined protocol (e.g., a specific number of rotations and / or a specific duration).

[0138] It will be appreciated that any suitable method can be used to dispense a sample into the sample preparation reservoir 202. For example, a sample can be dispensed directly into the sample preparation reservoir 202 without the use of a swab (e.g., by pipetting the sample). Liquid samples can include urine, blood, interstitial fluid, saliva, or any other suitable sample material. It will also be appreciated that embodiments of the present disclosure are not limited to liquid samples, and that any suitable sample, including solid and gas samples, can be added to the sample preparation reservoir 202.

[0139] In this exemplary implementation, the swab is then removed from the sample preparation reservoir 202 and discarded. The shipping cap 116 can then be threaded back onto the cartridge body 108. In another example, the shipping cap 116 is not threaded back onto the cartridge body 108.

[0140] The process then moves to block 804, where the cartridge 106 with the transport cap 116 attached is inverted or otherwise agitated to mix the fluid sample and disperse the sample within the sample preparation fluid in the sample preparation reservoir 202. When the cartridge 106 is positioned so that the end 120, including the threaded wall 404, faces upward (i.e., the cartridge 106 is not inverted), gravity can cause the fluid sample to collect bubble-free within the cylindrical chamber 206 of the sample preparation reservoir 202. After mixing, it may be desirable for the fluid sample to collect bubble-free within the cylindrical chamber 206 so that the intended volume of fluid can be dispensed into the sample preparation reservoir 202. In embodiments in which the transport cap 116 is not re-engaged to the cartridge body 108, block 804 can include mixing the fluid sample without inverting the cartridge body 108.

[0141] In certain examples, the sample preparation fluid may be heated before introducing the swab and mixing the sample into the sample preparation fluid. In other examples, the sample preparation fluid is heated after mixing with the sample. In embodiments in which the sample is added directly to the sample preparation reservoir 202, the sample may be added before or after heating the sample preparation solution. If present in the sample, particles containing the analyte of interest may be dissolved in the solution by the chemical action and / or temperature increase of the sample preparation fluid.

[0142] The process then moves to block 806, where the cartridge 106 is inserted into a diagnostic testing instrument. The sample in the sample preparation fluid then undergoes processing. The transport cap 116, if present, can be removed before or after the cartridge 106 is placed into the diagnostic testing instrument. The transport cap 116 does not include a locking tab that engages with the locking screw 412 on the cartridge body 108, and therefore cannot lock to the cartridge body 108 like the dispensing cap 114.

[0143] The process then moves to block 808, where the dispensing mechanism 102 is inserted into the sample preparation reservoir 202. The dispensing mechanism 102 is lowered vertically through the sample preparation reservoir 202 toward the seal 110a, until each piercing member 602 and each seal 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.

[0144] The process then moves to block 810 where the dispense cap 114 of the dispensing mechanism 102 engages with the sample preparation reservoir 202. In this example, it engages with the threaded wall 404 of the sample preparation reservoir 202.

[0145] Once the dispensing cap 114 has descended a certain distance along the threaded wall 404, the dispensing mechanism 102 reaches the position shown in FIG. 7C . The seal member 104 engages the tops of the two cylindrical chambers 206 formed by the inner surface 420 of the sample preparation reservoir 202. As the seal member 104 engages the tops of the two cylindrical chambers 206, the piercing member 602 is positioned above the seal 110a, which separates the sample preparation reservoir 202 from one or more diagnostic test reservoirs 204. The inner surface 420, the seal 110a, the seal member 104, and the piercing member 602 together define a predetermined volume of fluid. In the illustrated embodiment, these features define two fluidly separated predetermined volumes of fluid, each associated with one of the two cylindrical chambers 206. The seal member 104 forms a fluid seal against the inner surface 420, thereby confining a predetermined volume of fluid. Fluid present above the seal member 104 in the sample preparation reservoir 202 cannot enter the two cylindrical chambers 206 after the seal member 104 engages the inner surface 420.

[0146] In certain embodiments, the predetermined volume of fluid sealed within each cylindrical chamber 206 is up to 10 μL of liquid, up to 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 within or any range bounded by any of these ranges or numerical values. In some cases, values ​​outside of these numerical values ​​or ranges may also be used. Additionally or alternatively, in some embodiments, the predetermined volume of fluid is approximately 100 μL of liquid.

[0147] Next, the dispensing cap 114 is further rotated to move the dispensing mechanism 102 to reach the position shown in FIG. 7B. The piercing member 602 pierces the seals 110a and 110b between the sample preparation reservoir 202 and one or more diagnostic test reservoirs 204. Further movement causes the seal member 104 to slide along the inner surface 420 of the sample preparation reservoir 202, acting as a piston to form a sliding seal against the two cylindrical chambers 206 of the sample preparation reservoir 202. For example, a fluid-tight seal can be formed between the seal member 104 and the inner surface 420 within the two cylindrical chambers 206 of the sample preparation reservoir 202 as a result of the intimate contact between the seal member 104 and the inner surface 420.

[0148] The method then moves to block 812, where seals 110a, 110b are pierced and the downward movement of dispensing mechanism 102 forces a predetermined volume of fluid from within cylindrical chamber 206 into diagnostic test reservoir 204. This dispensing action forces the predetermined volume of fluid into diagnostic test reservoir 204. Seals 110a, 110b ensure that fluid communication does not occur between sample preparation reservoir 202 and one or more diagnostic test reservoirs 204 until a dispensing action occurs. When seal member 104 forms a seal with inner surface 420, fluid in the sample preparation reservoir above seal member 104 is not dispensed into one or more diagnostic test reservoirs 204. Thus, in embodiments of the disclosed systems and methods, a first portion of the total volume of fluid present in sample preparation reservoir 202 is dispensed into diagnostic test reservoir 204, while a second portion of the total volume of fluid present in sample preparation reservoir 202 is not dispensed into diagnostic test reservoir 204. In certain embodiments where there are two cylindrical chambers 206, each capable of dispensing approximately 100 μL, a volume of fluid greater than 500 μL may be present in sample preparation reservoir 202. In certain embodiments where there are two cylindrical chambers 206, each capable of dispensing approximately 100 μL, 1 to 3 mL of fluid may be present in sample preparation reservoir 202. In some embodiments, the total volume of fluid present in sample preparation reservoir 202 is 1 to 300 times the predetermined volume to be dispensed into diagnostic test reservoir 204. In some embodiments, the total volume of fluid present in sample preparation reservoir 202 is 5 to 50 times the predetermined volume to be dispensed into diagnostic test reservoir 204.

[0149] As previously described, the diagnostic test reservoir 204 includes one or more capillary grooves 304 configured to facilitate the flow of the predetermined volume of fluid from one end of the diagnostic test reservoir 204 (e.g., end 312 of the test vessel 112) toward the other end of the diagnostic test reservoir 304 (e.g., end 314 of the test vessel 112). Ensuring a consistent volume of fluid is dispensed into the diagnostic test reservoir 204 can reduce variability in assay results. Consistent and reliable dispensing of the predetermined volume of fluid to the bottom of the diagnostic test reservoir can ensure a higher likelihood that sufficient sample material (e.g., genomic material) is available for the assay reaction to ensure accurate assay results. Thus, in embodiments of the present disclosure, block 812 includes moving fluid along one or more capillary grooves 304 from the first end 434 toward the bottom 436 of the test vessel 112.

[0150] 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 vessel 112. Each receiving chamber of the test vessel 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 carry out 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 vessel 112.

[0151] In a non-limiting embodiment of the present disclosure, the dispensing mechanism 102 moves freely along the longitudinal axis of the sample preparation reservoir 202 until the locking tab engages the locking screw, as described in further detail below. Fluid within the sample preparation reservoir 202 flows relative to the dispensing mechanism 102 as the dispensing mechanism 102 is lowered along the longitudinal axis of the sample preparation reservoir 202. In a non-limiting example of the present disclosure, the dispensing mechanism 102 and the dispensing cap 114 are the only moving components of the diagnostic test instrument 100 during operation by a user. The entire dispensing mechanism 102 moves downward along the longitudinal axis of the diagnostic test reservoir 204 in a single motion until the entire movement of the dispensing mechanism 102 is stopped as described above. The downward movement of the dispensing mechanism 102 first defines (demarcates) a predetermined volume of fluid bounded 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. Further downward movement of the dispensing mechanism 102 then causes the piercing member 602 to pierce the seals 110a, 110b. Further downward movement of the dispensing mechanism 102 finally dispenses the predetermined volume of fluid sample into the diagnostic test reservoirs 204 due to the piston action of the dispensing mechanism with the seal formed by the sealing member 104. This dispenses the predetermined volume of fluid sample into a single diagnostic test reservoir 204.

[0152] Concurrent with the downward movement of the dispensing mechanism 102 along the longitudinal axis of the sample preparation reservoir 202, rotation of the dispense cap 114 about the longitudinal axis of the sample preparation reservoir 202 engages the locking screw 412 of the cartridge 106 with the locking tab 502 of the dispense cap 114. During the final rotation of the cap 114 to cause the piercing member 602 to pierce the seals 110a, 110b, the locking tab 502 on the dispense cap 114 rotates past the end of the locking screw 412. The locking screw 412 substantially prevents and / or inhibits rotational movement of the dispense cap 114 in either direction. This also substantially prevents and / or inhibits translational movement of the dispensing mechanism 102. It may be desirable for the locking screw 412 to remain locked to the top of the cartridge 106 so that the fluid within the sample preparation reservoir 202 remains sealed during and after the testing operation. Additionally, embodiments of this locking mechanism according to the present disclosure can advantageously lock the dispensing mechanism 102 in place, preventing further movement of liquid and / or reagents between the sample preparation reservoir 202 and the diagnostic test reservoir 204.

[0153] In the devices, systems, and methods according to the present disclosure, the dispensing mechanism 102 is a monolithic, single-piece structure that is the only moving component within the sample preparation reservoir 202. This reduces the likelihood of alignment errors during sealing of the seal members 104 and dispensing of fluid into the diagnostic test reservoir 204. In embodiments of the present disclosure, the (two) seal members 104 are easily aligned and securely seated within the two cylindrical chambers 206. There is a single stroke action that results in downward translation of the dispensing mechanism 102, which culminates in a dispensing operation. Advantageously, the consistent and reliable sealing performance of the seal members 104 during the dispensing operation contributes to a consistent and precise partial volume of fluid within the sample preparation reservoir 202 being dispensed into the diagnostic test reservoir 204. This may advantageously contribute to more consistent and accurate testing for the presence, absence, or amount of analyte within the fluid dispensed into the diagnostic test reservoir 204.

[0154] The method may then proceed to block 814, where the predetermined volume of fluid dispensed into the diagnostic test reservoir 204 rehydrates the lyophilized reagent if present in the diagnostic test reservoir 204. As previously mentioned, embodiments of the present disclosure may include a test vessel 112 having one or more capillary grooves 304, which may 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 will be understood that embodiments of the present disclosure are not limited to using dispensed fluid to rehydrate reagent or to providing reagent in the diagnostic test reservoir 204. Thus, in some non-limiting embodiments, the composition of the fluid dispensed into the diagnostic test reservoir 204 is the same as the composition of the fluid being tested for the presence, absence, or amount of analyte in the diagnostic test reservoir 204. In accordance with the present disclosure, the fluid and rehydrated reagent may be mixed within diagnostic test reservoir 204. In some embodiments, beads, such as magnetic beads, contained in the lyophilized reagent may be agitated to facilitate mixing in diagnostic test reservoir 204. In such embodiments, mixing with the beads may continue as the reaction proceeds according to block 816 or as detection occurs according to block 818.

[0155] Once the reagents are rehydrated, the method proceeds to block 816, where a reaction is carried out in the amplification fluid in the diagnostic test reservoir 204. The reaction may include an amplification reaction. The reaction may include an assay. The reaction may include applying heat to the diagnostic test reservoir 204, where the heat is transferred to the fluid to promote an isothermal amplification reaction. In other cases, the amplification reaction includes cyclic heating steps to carry out the amplification reaction. It will be understood that these exemplary reactions and assays are not limiting, and any suitable reaction may be carried out in the fluid in the diagnostic test reservoir 204.

[0156] The method ends at block 818. At block 818, the presence or absence of the analyte is detected. The analyte may be detected as the amplification reaction progresses (e.g., during a real-time PCR test) or at the end of the amplification reaction. The presence or absence (presence or absence) of the analyte may be detectable, for example, via a fluorescent signal generated during the amplification reaction. Advantageously, embodiments of the present disclosure that include a test vessel 112 having one or more capillary grooves 304 can detect the presence, absence, and in some cases the amount, of an analyte with greater specificity and / or sensitivity.

[0157] [How to use diagnostic test equipment in diagnostic test machines] In some embodiments, the diagnostic testing device 100 may be introduced into the diagnostic testing machine 900 before or after a dispensing operation as described herein has been performed. The device 100 may be inserted into one or more heat blocks 902, 904 of the diagnostic testing machine 900 configured to accept the diagnostic testing device 100. The diagnostic testing device 100 with the shipping cap 116 or dispensing cap 114 may be inserted into the diagnostic testing machine 900.

[0158] In one non-limiting embodiment, the diagnostic testing machine 900 applies heat to the amplification fluid in the diagnostic test reservoir 204 using a heat block 902 to carry out an amplification reaction. The diagnostic testing machine 900 also sends and receives optical signals to and from the diagnostic test reservoir 204 to detect analytes, if present, in the amplification fluid in the diagnostic test reservoir 204. The diagnostic testing machine 900 may use one or more image sensors (not shown) to optically scan a portion of the test vessel 112, such as the bottom 436 of the test vessel 112. Such scanning may be used to detect and / or measure positive control reporters in the amplification fluid. Measurement of the positive control reporters may confirm the dispensing operation and may confirm that the amplification reaction is able to proceed as intended. Such scanning may also be used to detect and / or measure the progress of the test assay reaction. For example, the diagnostic tester 900 may optically scan the bottom of the diagnostic test reservoir 204 and detect and / or measure changes in fluorescence indicative of an ongoing amplification reaction due to the presence of analyte. As previously mentioned, embodiments of the present disclosure are not limited to real-time detection during the reaction, and in some cases, detection occurs when the reaction is complete.

[0159] 9 shows a cross-sectional view of a diagnostic testing device 100 housed within one or more heat blocks 902, 904 of a diagnostic testing machine 900. The diagnostic testing device 100 includes a dispensing mechanism 102 housed within a sample preparation reservoir 202. In this non-limiting example, a test container 112 is housed within a first heat block 902 of the diagnostic testing machine 900, and the sample preparation reservoir 202 is housed within a second heat block 904 of the diagnostic testing machine 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 within the fluid within the sample preparation reservoir of the cartridge body 108. When the cartridge body 108 is heated, the fluid contained within the sample preparation reservoir 202 can be heated. After a partial volume of fluid in sample preparation reservoir 202 is dispensed into test vessel 112, heat block 902 may apply heat to test vessel 112 to carry out an amplification reaction in the amplification fluid present in test vessel 112. A window (not shown in this cross-sectional view) in heat block 902 may allow optical signals to be sent to and received from one or more diagnostic test reservoirs 204 to detect analytes if present in the amplification fluid.

[0160] One or more optical sensors incorporated within the diagnostic tester 900 may capture fluorescent signals emitted from the amplification fluid during or after the amplification reaction. Digital outputs from the one or more image sensors may be used to verify the progress of the test assay and confirm the correct release and flow of test reagents within the cartridge, and the integrity of the test may be verified by the controller and utilized to improve the reliability and accuracy of the test results.

[0161] Figures 10-18 show perspective, front, back, left, right, plan, bottom, top exploded, and bottom exploded views, respectively, of diagnostic test device 100, including cartridge body 108, test reservoir 112, and dispensing cap 114. As previously described with reference to Figures 3A-3C, 3F-3H, and 4H, test reservoir 112 includes capillary groove 304.

[0162] [Manually operated, visually read, non-instrument operated diagnostic testing equipment] In some applications, the diagnostic testing device 100 can be used manually without an instrument. For example, in some embodiments, the diagnostic testing device 100 is held in one hand while the transport cap 116 is removed with the other hand, a sample is added, the dispensing mechanism 102 is inserted into the cartridge body 108, and the dispensing cap 114 is engaged with the cartridge body 108 and rotated closed. In some such embodiments, if the diagnostic testing reservoir 204 is visually clear, dispensing of fluid into the diagnostic testing reservoir 204 can be visually observed, and a color or turbidity change can be observed over time to provide a diagnostic test readout or indication. This approach takes advantage of operating with a fully sealed cartridge 106 upon sample addition, and of dispensing a measured volume of prepared sample fluid internally into the diagnostic testing reservoir 204 without the use of external fluid transfer steps.

[0163] Optionally, a stand may be provided to support the diagnostic test device 100 for the purposes of removing the transport cap 116, adding the sample, inserting the dispensing mechanism 102, and fitting the dispensing cap 114 to the cartridge body 108 to lock it closed.

[0164] Optionally, a heater block may be provided to provide temperature control of the sample preparation reservoir 202 and the diagnostic test reservoirs 204 of the diagnostic test instrument 100, but the diagnostic test instrument 100 is manually withdrawn to observe visible test results in one or more diagnostic test reservoirs 204. In some applications, the heater block may include a window that allows viewing of the diagnostic test reservoirs 204. In such applications, the diagnostic test instrument 100 does not need to be withdrawn from the heater block to observe the test results.

[0165] [term] Features referred to herein as "capillary grooves" may also be referred to as "capillary channels" and / or "capillary indentations." As a non-limiting example, a groove may be a long, narrow cut or depression made specifically to guide movement.

[0166] Conjunctions such as "at least one of X, Y, and Z," unless specifically stated otherwise or understood otherwise within the context, are generally intended to convey that an item, term, etc. can be either X, Y, or Z. Thus, such conjunctions are generally not intended to indicate that a particular embodiment requires the presence of at least one of X, at least one of Y, and at least one of Z.

[0167] As used herein, degrees such as "generally," "about," "generally," and "substantially" refer to a value, amount, or characteristic that is close to a stated value, amount, or characteristic and still performs a desired function or achieves a desired result. For example, the terms "generally," "about," "generally," and "substantially" can refer to an amount that is within 10%, 5%, 1%, 0.1%, and 0.01% of the stated amount.

[0168] The term "and / or" as used herein has its broadest, non-limiting meaning and means that the disclosure includes A only, B only, both A and B, or alternatively, A or B, but does not require both A and B, or one of A, or one of B. As used herein, the phrase "at least one of" A, B "and" C should be interpreted to mean the logical A or B or C, using a non-exclusive logical OR.

[0169] Conditional language used herein, such as "can," "could," "might," and "may," is generally intended to convey that certain features, elements, and / or steps are optional, unless specifically stated otherwise or understood otherwise within the context. Thus, such conditional language is not generally intended to indicate that the features, elements, and / or steps are required in any manner. Terms such as "comprising," "include," and "have" are used in an inclusive and open-ended manner and do not exclude additional elements, features, actions, operations, etc. Additionally, the term "or" is used in an inclusive (as opposed to exclusive) sense; for example, when used to connect a list of elements, the term "or" may refer to one, some, or all of the elements in the list.

[0170] Any method disclosed herein does not have to be performed in the order described. The methods disclosed herein include specific actions to be performed by a practitioner, but may also include third-party instructions regarding those actions, whether explicit or implicit.

[0171] Some or all of the methods and tasks described herein may be performed by a computer system and may be fully automated. A diagnostic test system according to the present disclosure may, in some cases, comprise a computer system that may include multiple distinct computers or computing devices (e.g., physical servers, workstations, storage arrays, cloud computing resources, etc.) that communicate and interoperate over a network to perform the described functions. Each such computing device typically includes a processor (or multiple processors) that executes program instructions (instructions) or modules stored in memory or other non-transitory computer-readable storage media or devices (e.g., solid-state storage devices, disk drives, etc.). Various functions disclosed herein may be embodied in such program instructions and / or implemented in the computer system's application-specific circuitry (e.g., ASIC or FPGA). When a computer system includes multiple computing devices, these devices may, but need not, be co-located. The results of the methods and tasks of the present disclosure may be persistently stored by converting physical storage devices, such as solid-state memory chips and / or magnetic disks, to a different state. The computer system may be a cloud-based computing system whose processing resources are shared by multiple distinct business entities or other users.

[0172] While the foregoing detailed description illustrates, describes, and points out novel features, it will be understood that various omissions, substitutions, and changes may be made in the form and details of the devices, systems, and methods without departing from the spirit of the disclosure. As will be recognized, certain portions of the description herein may be embodied in a form that does not provide all of the features and advantages described herein, since some features may be used or practiced in isolation from other features. Consequently, the disclosure is not intended to be limited to the particular embodiments disclosed herein, but rather to cover all modifications and alternatives that fall within the true scope and spirit of the disclosure.

Claims

1. a cartridge body containing a sample preparation reservoir; a diagnostic test reservoir coupled to the cartridge body and having at least one chamber and one or more capillary grooves along an interior surface of the at least one chamber; Equipped with the at least one chamber configured to receive fluid from the sample preparation reservoir in a first section of the at least one chamber; The one or more capillary grooves are configured to facilitate flow of the fluid toward the second section of the at least one chamber.

1. A diagnostic test device comprising:

2. The one or more capillary grooves are configured to inhibit droplets of the fluid from adhering to the interior surface of the first section of the at least one chamber when the fluid is dispensed from the sample preparation reservoir into the at least one chamber.

2. The diagnostic test device of claim 1.

3. The one or more capillary grooves are configured to increase the volume of the fluid collected in the second section of the at least one chamber.

3. A diagnostic test device according to claim 1 or 2.

4. The at least one chamber is configured to transmit a fluorescent signal.

4. A diagnostic test device according to any one of claims 1 to 3.

5. The flow of the fluid is downward from the first section to the second section.

5. A diagnostic test device according to any one of claims 1 to 4.

6. The second section has a closed end.

6. A diagnostic test device according to any one of claims 1 to 5.

7. a seal between the sample preparation reservoir and the at least one chamber; Further provided with The seal is configured to prevent transfer of the fluid between the sample preparation reservoir and the at least one chamber.

7. A diagnostic test device according to any one of claims 1 to 6.

8. a dispensing mechanism configured to break the seal and allow movement of the fluid from the sample preparation reservoir into the at least one chamber.

8. The diagnostic test device of claim 7, further comprising:

9. the diagnostic test device includes the fluid; The fluid comprises an aqueous buffer solution.

9. A diagnostic test device according to any one of claims 1 to 8.

10. The aqueous buffer solution contains at least one of RBCC, GRBS, and SDS.

10. The diagnostic test device of claim 9.

11. The sample preparation reservoir is configured to receive a test sample.

10. The diagnostic test device of claim 9.

12. the sample preparation reservoir is configured to receive a swab containing the test sample; At least a portion of the fluid and at least a portion of the test sample are configured to move from the sample preparation reservoir to the at least one chamber.

12. The diagnostic test device of claim 11.

13. the at least one chamber includes two diagnostic test reservoirs; Each of the diagnostic test reservoirs includes one or more capillary channels.

13. Diagnostic test apparatus according to any one of claims 1 to 12.

14. the at least one chamber comprises plastic 14. Diagnostic test apparatus according to any one of claims 1 to 13.

15. The plastic includes polypropylene 15. The diagnostic test device of claim 14.

16. The at least one chamber is coupled to the cartridge body via ultrasonic welding.

16. Diagnostic test device according to claim 14 or 15.

17. The one or more capillary channels are configured to facilitate movement of the fluid in contact with the lyophilized reagent within the second section of the at least one chamber.

17. Diagnostic test apparatus according to any one of claims 1 to 16.

18. The freeze-dried reagent includes a nucleic acid amplification primer and a nucleic acid amplification detection probe.

20. The diagnostic test device of claim 17.

19. the one or more capillary grooves have a plurality of spaced apart valleys along the interior surface of the at least one chamber; Each of the plurality of spaced valleys has a curved cross section.

19. Diagnostic test apparatus according to any one of claims 1 to 18.

20. The curved cross section comprises a smooth arc.

20. The diagnostic test device of claim 19.

21. Each of the plurality of spaced valleys has three inflection points.

21. Diagnostic test device according to claim 19 or 20.

22. Each of the plurality of spaced valleys has three curvatures.

22. Diagnostic test device according to any one of claims 19 to 21.

23. Each of the plurality of spaced valleys has two protrusions separated by a recess.

23. Diagnostic test device according to any one of claims 19 to 22.

24. a transition between the inner surface of the at least one chamber and the plurality of spaced valleys having rounded edges; 21. Diagnostic test device according to claim 19 or 20.

25. One of the plurality of spaced apart valleys has a semicircular or semi-elliptical cross-sectional shape.

25. Diagnostic test apparatus according to any one of claims 19 to 24.

26. The plurality of spaced-apart valleys are separated by flat portions of the interior surface of the at least one chamber.

26. Diagnostic test device according to any one of claims 19 to 25.

27. a portion of the inner surface of the second section of the at least one chamber forming a continuous circumferential surface; 27. Diagnostic test device according to any one of claims 19 to 26.

28. A portion of the interior surface of the second section of the at least one chamber forms a continuous curved surface.

28. Diagnostic test device according to any one of claims 19 to 27.

29. The inner surface forms a closed periphery within the at least one chamber.

29. Diagnostic test device according to any one of claims 19 to 28.

30. A portion of the inner surface terminates in a smooth arc within the second section of the at least one chamber.

30. Diagnostic test device according to any one of claims 19 to 29.

31. a portion of the inner surface is 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.

31. The diagnostic test device of claim 30.

32. The at least one chamber further includes a window area below ends of the plurality of spaced valleys.

32. Diagnostic test device according to any one of claims 19 to 31.

33. The at least one chamber further includes a window region that does not include any of the plurality of spaced valleys.

32. Diagnostic test device according to any one of claims 19 to 31.

34. One of the plurality of spaced valleys is tapered along a portion of its height.

34. Diagnostic test device according to any one of claims 19 to 33.

35. The one valley of the plurality of spaced valleys begins to taper at a height between the first section and the second section.

35. The diagnostic test device of claim 34.

36. an end of one of the plurality of spaced valleys having a semicircular profile; 35. Diagnostic test device according to any one of claims 19 to 34.

37. an end of one of the plurality of spaced valleys having a tapered profile; 36. A diagnostic test device according to any one of claims 19 to 35.

38. a first valley of the plurality of spaced valleys extending a first distance toward the second section of the at least one chamber; a second valley of the plurality of spaced valleys extending a second distance toward the second section of the at least one chamber; The second distance is greater than the first distance.

38. Diagnostic test device according to any one of claims 19 to 37.

39. a valley of the plurality of spaced valleys having 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; 39. Diagnostic test device according to any one of claims 19 to 38.

40. 1. A method of performing a diagnostic test using a diagnostic test device, comprising: the diagnostic testing device includes a sample preparation reservoir and a diagnostic testing reservoir; The method comprises: dispensing fluid from the sample preparation reservoir into at least one chamber of the diagnostic test reservoir; conducting an amplification reaction in said at least one chamber; detecting the presence or absence of an analyte in said at least one chamber; Equipped with one or more capillary grooves along an interior surface of the at least one chamber; The one or more capillary grooves are configured to facilitate flow of the fluid toward a section of the at least one chamber. A method characterized by:

41. adding a test sample to the fluid in the sample preparation reservoir prior to dispensing the fluid into the at least one chamber.

41. The method of claim 40 further comprising:

42. rehydrating the lyophilized reagent in the at least one chamber with the fluid dispensed from the sample preparation reservoir.

42. The method of claim 40 or 41, further comprising:

43. conducting the amplification reaction includes applying heat to the at least one chamber; 43. A method according to any one of claims 40 to 42.

44. detecting the presence or absence of the analyte comprises detecting a change in fluorescence emission indicative of a test result; the fluorescent emission exits the at least one chamber through a portion of a wall of the chamber; The portion of the wall does not include a capillary groove.

44. A method according to any one of claims 40 to 43.

45. distributing the fluid includes collecting the fluid within the section of the at least one chamber; The one or more capillary grooves are configured to increase the volume of the fluid collected within the section of the at least one chamber.

45. A method according to any one of claims 40 to 44.

46. causing the fluid to flow along the one or more capillary channels toward the section of the at least one chamber.

46. ​​The method of any of claims 40 to 45, further comprising:

47. the one or more capillary grooves have a plurality of spaced apart valleys along the interior surface of the at least one chamber; Each of the plurality of spaced valleys has a curved cross section.

47. A method according to any one of claims 40 to 46.

48. The curved cross section comprises a smooth arc.

48. The method of claim 47.

49. Each of the plurality of spaced valleys has three inflection points.

49. The method of claim 47 or 48.

50. Each of the plurality of spaced valleys has three curvatures.

50. The method of any one of claims 47 to 49.

51. Each of the plurality of spaced valleys has two protrusions separated by a recess.

51. A method according to any one of claims 47 to 50.

52. a transition between the inner surface of the at least one chamber and the plurality of spaced valleys having rounded edges; 52. The method of claim 47 or 51.

53. One of the plurality of spaced apart valleys has a semicircular or semi-elliptical cross-sectional shape.

53. A method according to any one of claims 47 to 52.

54. The plurality of spaced-apart valleys are separated by flat portions of the interior surface of the at least one chamber.

54. A method according to any one of claims 47 to 53.

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