DIAGNOSTIC TEST DEVICE WITH INTERNAL CYLINDER AND PLUNGER - Patent application

Abstract

A diagnostic testing device for performing testing of biological or environmental samples is provided. In one embodiment, the diagnostic testing device includes a sample preparation reservoir, a dispensing mechanism including a seal member and a piercing member, and at least one diagnostic testing reservoir separated from the sample preparation reservoir by a seal. When the seal member engages a side of the at least one chamber, a predetermined amount of fluid is defined between the seal member, the piercing member, a side of the at least one chamber defined by the sample preparation reservoir, and the seal. The piercing member breaks the at least one seal to dispense the predetermined amount of fluid into the at least one diagnostic testing reservoir. The seal member is configured to directly contact the side of the at least one chamber when the seal is broken.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 63 / 241,033, filed September 6, 2021, which is incorporated by reference in its entirety.

[0002] The present disclosure relates to devices, systems and methods for performing testing of a sample-containing fluid. In particular, the devices, systems and methods of the present disclosure relate to devices configured to receive a sample for performing diagnostic testing or analysis of a biological, chemical or environmental sample and determine the presence and / or amount of one or more analytes of interest in the sample. The analytes can be detected, for example, using DNA or RNA amplification when the device is received into a testing system. Devices according to the present disclosure can include consumable devices for diagnostic testing, such as disposable containers that receive the sample, contain the sample before and during the diagnostic test, and are discarded after the diagnostic test is completed. [Background technology]

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

[0004] Nucleic acid amplification can generate many copies of a target genetic sequence in a test solution. As part of the test assay, specific markers can be designed to link to the target sequence. These markers can provide a detectable signal, such as a light signal, from the test solution upon binding. The change in the light 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 comprised of a florescence quencher that approximates a fluorescent atom or array of atoms. The marker molecule can be configured such that upon selective binding to a target nucleic acid sequence, the quencher and the fluorophore are separated, resulting in a detectable fluorescent signal due to the action of the fluorophore. In this 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 and relative amount of a target material or analyte of interest in the sample being tested.

[0005] A single test well can contain two or more markers, each of which can provide a light output based on binding to a different target nucleic acid sequence. Different sensors, or sensors with two or more selective outputs, can also be used in conjunction with these two or more markers. For example, in a two-channel system, two different fluorescent dyes can be used and detected by two different fluorescent sensors configured to detect the emission of each fluorescent dye in its respective frequency range. In this way, the two channels can be distinguished.

[0006] Such an approach can be used to provide a control channel. In one example control channel, the test assay chemistry is configured such that a control target, such as a synthetic nucleic acid sequence, should be present whenever the test process is performed correctly. The output of the control channel can be used to verify that the system has performed the test process correctly 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, with each well capable of running a different amplification chemistry and / or a different set of target markers. The control channel described above can be operated in one or more of the wells. Summary of the Invention [Problem to be solved by the invention]

[0008] In some approaches, the test sample is not sealed from the environment during the process of preparing and transferring the sample to a test container in the test meter. This exposure of the sample can pose an infection risk to users and others, as well as contaminate the test meter and testing area, resulting in inaccurate diagnostic results for subsequent tests. Additionally, such exposure can also contaminate the test sample itself. [Means for solving the problem]

[0009] The devices, systems and methods of the present disclosure each have multiple innovative aspects, no single one of which is solely responsible for its desirable attributes, and without limiting the scope of the disclosure, its more prominent features will now be discussed briefly.

[0010] In one embodiment, a device is provided. The device includes a sample preparation reservoir capable of receiving a sample at a first end and including an inner surface at a second end that defines a side of at least one chamber. The device includes at least one diagnostic test reservoir. The device includes at least one seal disposed between the sample preparation reservoir and the at least one diagnostic test reservoir. The device includes a dispensing mechanism that can be inserted into the first end of the sample preparation reservoir and translated toward the second end of the sample preparation reservoir, the dispensing mechanism including a piercing member and a sealing member. The sealing member can engage a side of the at least one chamber when the dispensing mechanism translates toward the second end of the sample preparation reservoir to define a predetermined amount of fluid between the sealing member, the piercing member, the side of the at least one chamber at the second end of the sample preparation reservoir, and the at least one seal when the sealing member engages the side of the at least one chamber. The piercing member can pierce the at least one seal after a predetermined volume has been determined, and the seal member and piercing member can dispense the determined volume from the sample preparation reservoir to the at least one diagnostic test reservoir after the seal has been pierced.

[0011] The seal member can be configured to directly contact an inner surface defining a side of the at least one chamber when the dispensing mechanism translates toward the second end of the sample preparation reservoir.

[0012] In some embodiments, the piercing member does not move relative to the sealing member when the determined volume is dispensed into the at least one diagnostic test reservoir.

[0013] The piercing member may include at least one spike rod and the sealing member may include at least one gasket surrounding the at least one spike rod.

[0014] In some embodiments, a single action of translating the dispensing mechanism toward the second end of the sample preparation reservoir can (a) define a predetermined amount of fluid between the sealing member, the piercing member, the side of the at least one chamber, and the at least one seal, (b) pierce the at least one seal, and (c) dispense the determined amount into at least one diagnostic test reservoir.

[0015] The sample preparation reservoir, the at least one diagnostic test reservoir and the at least one seal can be connected to form a joint structure.

[0016] The inner surface at the second end of the sample preparation reservoir can define at least one cylindrical chamber.

[0017] The interior surface at the second end of the sample preparation reservoir can define at least two cylindrical chambers.

[0018] The device can include a notch in a portion of the inner surface between the two cylindrical chambers, the predetermined amount being defined at least in part by a depth of the notch.

[0019] The seal member can be configured to directly contact the lower inner surface of the at least one chamber when the determined volume has been dispensed from the sample preparation reservoir into the at least one diagnostic test reservoir.

[0020] The inner surface at the second end of the sample preparation reservoir can define two cylindrical chambers, each of the two cylindrical chambers configured to dispense a predetermined amount of fluid. The piercing member can include two spike rods. The sealing member can include a gasket surrounding each of the two spike rods. The device can include a test vessel including two diagnostic test reservoirs, each diagnostic test reservoir configured to receive a predetermined amount of fluid from one of the two cylindrical chambers.

[0021] The inner surface at the second end of the sample preparation reservoir can define four chambers, and the device can include four diagnostic test reservoirs.

[0022] The seal member may include an elastomeric material.

[0023] The piercing member may include one or more spikes, each of which may include a cross-shaped cross-section including a concave surface and a chamfered surface.

[0024] The sample preparation reservoir can contain a sample preparation fluid.

[0025] The at least one seal can include a first seal configured to seal the second end of the sample preparation reservoir and a second seal configured to seal the diagnostic test reservoir.

[0026] At least one of the seals may include a foil.

[0027] The sample preparation reservoir can be configured to receive a swab containing the sample.

[0028] The second end of the sample preparation reservoir can include a lip configured to be joined to the diagnostic test reservoir.

[0029] The sample preparation reservoir can be configured to contain a volume of fluid ranging from 1 to 3 mL, with the predetermined volume ranging from 10 μL to 1 mL.

[0030] The sample preparation reservoir can be configured to contain a volume of fluid that is 1-300 times greater than the predetermined volume.

[0031] The sample preparation reservoir can be configured to accommodate a fluid volume of 1-3 mL, with the predetermined volume being approximately 100 µL.

[0032] The dispensing mechanism may include a cap configured to engage a first end of the sample preparation reservoir. The cap may be configured to rotate relative to the piercing member. The first end of the sample preparation reservoir may include threads configured to engage threads of the cap. The cap may be configured to lock to the first end of the sample preparation reservoir to prevent substantial movement of the cap relative to the sample preparation reservoir. The cap may include a plug seal configured to engage a top end of the sample preparation reservoir. The plug seal may be configured to prevent fluid flow when engaged with a top end of the sample preparation reservoir.

[0033] In another embodiment, a diagnostic testing apparatus configured to receive the device is provided.

[0034] In yet another embodiment, a method of performing a diagnostic test using a diagnostic test device is provided. The diagnostic test device can include a sample preparation reservoir and at least one diagnostic test reservoir. The sample preparation reservoir can include a first end and an inner surface at a second end that defines a side of at least one chamber. The method can include introducing a sample to a fluid in the sample preparation reservoir at the first end of the sample preparation reservoir. The method can include dispensing a predetermined amount of fluid from the sample preparation reservoir to the at least one diagnostic test reservoir. Dispensing the predetermined amount of fluid can include inserting a dispensing mechanism into the first end of the sample preparation reservoir and translating the dispensing mechanism toward the second end of the sample preparation reservoir. Dispensing the predetermined amount of fluid can include engaging a seal member of the dispensing mechanism with a side of the at least one chamber to define a predetermined amount between the seal member, a piercing member of the dispensing mechanism, the inner surface that defines a side of the at least one chamber, and at least one seal between the sample preparation reservoir and the at least one diagnostic test reservoir. Dispensing the predetermined amount of fluid can include piercing at least one seal between the sample preparation reservoir and the at least one diagnostic test reservoir with a piercing member of the dispensing mechanism. The method can include performing an amplification reaction in the at least one diagnostic test reservoir. The method can include detecting the presence or absence of the analyte of interest in the at least one diagnostic test reservoir.

[0035] Engaging the seal member and determining the predetermined amount may occur simultaneously.

[0036] The inner surface at the second end of the sample preparation reservoir can define two cylindrical chambers, each of the two cylindrical chambers configured to dispense a predetermined amount of fluid. The piercing member can include two spike rods. The sealing member can include a gasket surrounding each of the two spike rods. The diagnostic testing device can include two diagnostic testing reservoirs. A predetermined amount of fluid can be dispensed from each of the two cylindrical chambers into one of the diagnostic testing reservoirs.

[0037] The inner surface at the second end of the sample preparation reservoir can define four cylindrical chambers. The device can include four diagnostic test reservoirs.

[0038] The seal member can directly contact the lower inner surface of the at least one chamber after a predetermined volume of fluid is dispensed from the sample preparation reservoir to the at least one diagnostic test reservoir.

[0039] Translation of the dispensing mechanism can be stopped by locking the dispensing mechanism in place relative to the sample preparation reservoir.

[0040] Locking can include engaging locking threads of the diagnostic testing device with a locking tab of the cap of the dispensing mechanism. Locking can further include engaging a blocking flange of the diagnostic testing device with an over-travel tab of the cap of the dispensing mechanism.

[0041] The amount of fluid can begin to be dispensed into the at least one diagnostic test reservoir before the at least one seal is completely pierced.

[0042] The method can include rehydrating a lyophilized reagent in the diagnostic test reservoir with a predetermined amount of fluid. The lyophilized reagent can include a nucleic acid amplification primer. The lyophilized reagent can include a nucleic acid amplification detection probe.

[0043] Performing an amplification reaction in the at least one diagnostic test reservoir can include applying heat to the at least one diagnostic test reservoir.

[0044] Detecting the presence or absence of the analyte can include measuring an optical signal from the at least one diagnostic test reservoir. Measuring the optical signal can include measuring fluorescence from the at least one diagnostic test reservoir.

[0045] The method can further include engaging the diagnostic testing device with a diagnostic testing apparatus configured to perform an amplification reaction to detect the presence or absence of the analyte of interest. Engaging the diagnostic testing device can include heating the sample preparation reservoir.

[0046] The above-mentioned aspects, as well as other features, aspects, and advantages of embodiments of the present disclosure, are described in connection with various implementations below with reference to the accompanying drawings. The illustrated implementations are by way of example only and are not intended to be limiting. Throughout the drawings, like symbols typically identify like components unless otherwise dictated by context. [Brief description of the drawings]

[0047] [Figure 1] 1 is an exploded view of components of an example diagnostic testing device according to the present disclosure. [Diagram 2] FIG. 2 shows the example diagnostic test device of FIG. 1 with a dispensing cap. [Diagram 3] FIG. 2 shows the example diagnostic test device of FIG. 1 with a shipping cap. [Figure 4A] FIG. 2 is a diagram of a cartridge body of the embodiment shown in FIG. 1. [Figure 4B] FIG. 4B is a view of a cylindrical chamber of the embodiment shown in FIG. 4A. [Figure 4C] FIG. 4B is a cross-sectional view of the cylindrical chamber shown in FIG. 4A. [Figure 4D] FIG. 4B is a cross-sectional view of the cartridge body of the embodiment shown in FIG. 4A. [Figure 4E] FIG. 4B is a cross-sectional view of the cartridge body of the embodiment shown in FIG. 4A. [Figure 4F] FIG. 4B is a side view of the cartridge body of the embodiment shown in FIG. 4A. [Figure 4G] FIG. 4B is a top-down view of the cartridge body of the embodiment shown in FIG. 4A. [Figure 4H] FIG. 2 is an enlarged view of the cuvette in FIG. 1. [Figure 5A] FIG. 2 shows the dispensing cap of FIG. 1. [Figure 5B] 1 is a cross-sectional view of another dispensing cap according to the present disclosure. [Figure 5C] 5C is a cross-sectional view of the dispensing cap of FIG. 5B engaged with the cartridge body of the embodiment of FIG. 1. [Figure 5D] 2 illustrates the interaction of the locking tab of the dispensing cap of FIG. 1 with the locking threads of the cartridge body of FIG. 1. [Figure 5E] 2 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. 1. [Figure 6A] FIG. 2 is a side view of the dispensing mechanism of FIG. 1. [Figure 6B] FIG. 2 is a bottom perspective view of the dispensing mechanism of FIG. 1. [Figure 6C] 13A-13C show another embodiment of a seal member according to the present disclosure. [Figure 6D] 13A-13C show another embodiment of a seal member according to the present disclosure. [Figure 6E] FIG. 6E is a top view of another embodiment of the seal member shown in FIGS. 6C and 6D. [Figure 6F] FIG. 6E is a bottom view of another embodiment of the seal member shown in FIGS. 6C and 6D. [Figure 7A] FIG. 2 is a cross-sectional view of the embodiment of FIG. 1 with a dispensing mechanism inserted into the sample preparation reservoir. [Figure 7B] 2 is a cross-sectional view of the embodiment of FIG. 1 with the dispensing mechanism piercing the seal. [Figure 7C] 2 is a cross-sectional view of the embodiment of FIG. 1 in which the seal member engages the wall of the cylindrical chamber but does not pierce the seal. [Figure 7D] 7C is a cross-sectional view of the embodiment of FIG. 1 with the dispensing mechanism fully inserted to dispense a predetermined amount of fluid into the diagnostic test reservoir, showing the piercing member in greater detail than FIG. 7E. [Figure 7E] 2 is a cross-sectional view of the embodiment of FIG. 1 showing the entire diagnostic test device with the dispensing mechanism fully inserted to dispense a predetermined amount of fluid into the diagnostic test reservoir. [Figure 8] FIG. 1 illustrates an example method for performing a diagnostic test using a diagnostic test device according to the present disclosure. [Figure 9] FIG. 2 illustrates the diagnostic test device of FIG. 1 received in a portion of a diagnostic testing apparatus. [Figure 10] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 11] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 12] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 13] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 14] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 15] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 16] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 17] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 18] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 19] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 20] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 21] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 22] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Diagram 23] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 24] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Diagram 25] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 26] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 27] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 28] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 29] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Diagram 30] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Diagram 31] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Diagram 32] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Diagram 33] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Diagram 34] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Diagram 35] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Diagram 36] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 37] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 38] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 39] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Diagram 40] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Diagram 41] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Diagram 42] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Diagram 43] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Diagram 44] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Diagram 45] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Diagram 46] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 47] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 48] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 49] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 50] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 51] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 52] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 53] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 54] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 55] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 56] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 57] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 58] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 59] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 60] 1 is a diagram of an example diagnostic testing device according to the present disclosure. [Figure 61] 1 is a diagram of an example diagnostic testing device according to the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0048] The embodiments of the present disclosure provide devices, systems and methods for sequentially transferring a predetermined amount 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 can include a test sample in a buffer. In some cases, the fluid sample is ready for amplification when it is transferred from the first portion of the device to the second portion. The first portion of the diagnostic testing device can include a sample preparation reservoir and the second portion of the diagnostic testing device can include one or more test vessels. For example, a predetermined amount of the fluid sample can be transferred from a sample processing reservoir to one or more test vessels that contain pre-stored amplification reagents. The sample processing device can include a dual internal cylinder and a plunger can be used to dispense a predetermined amount of the fluid sample through the dual internal cylinder into the two test vessels. The test vessels are sealed against the external environment and the sample preparation reservoir before the transfer of the fluid sample and are therefore protected from contaminants. The test vessels remain sealed against the external environment after the transfer of the fluid sample. It is advantageous that the external environment is not exposed to the fluid sample, which may contain hazardous components.

[0049] The diagnostic testing device of the present disclosure can dispense a predetermined amount of the fluid sample simultaneously with the sample receiving end of the sample preparation reservoir being sealed. For example, the action of twisting a cap engaged with the sample receiving end of the sample preparation reservoir can also dispense the fluid sample from the sample preparation reservoir to the test vessel. When dispensing the fluid sample, the cap can lock to prevent access to the sample preparation reservoir and the test vessel to protect them from contamination. Further fluid flow between the sample preparation reservoir and the test vessel is also prevented. The mechanism for dispensing the fluid sample and sealing the diagnostic testing device simultaneously is not complex and involves the movement of a single component within the sample processing reservoir. Specifically, the dispensing mechanism includes a plunger that is configured to translate within the sample preparation reservoir to directly contact an inner surface of the sample processing reservoir as the piercing end of the plunger pierces one or more seals separating the sample preparation reservoir and the test vessel. Once dispensed, the fluid sample within the test vessel can be analyzed to determine the presence or absence of a target analyte, for example, using an amplification reaction. The diagnostic test device of the present disclosure has the advantage of reliably dispensing precise volumes of a fluid sample from a single sample preparation reservoir into two or more test vessels containing different reagents, allowing multiple testing of a single sample.

[0050] Embodiments of the present disclosure provide devices, systems, and methods that allow for test sample preparation followed by testing, for example, by amplification in conjunction with a fluorescent marker. Certain embodiments include a diagnostic test assembly (also referred to herein as a "cartridge") for use with a diagnostic test meter to perform diagnostic testing of biological or environmental samples. Such a cartridge can be used with a diagnostic testing device (also referred to herein as an "instrument"). As described herein, the cartridge is easily operable by a user without the need for typical laboratory equipment.

[0051] Throughout the following description, various embodiments are described with reference to an example implementation of a rapid nucleic acid-based diagnostic system capable of testing for a variety of diseases. As an illustrative example, the system can test for Sexually Transmitted Infections (STIs), such as gonorrhea and chlamydia, and Respiratory Tract Infections (RTIs), such as influenza A or B. This example system targets the point-of-care (POC) market, where ease of use, simplicity, CLIA waivability, and rapid turnaround time (TAT) of result are considerations. However, it will be understood that any of the devices, systems, and methods described herein may also be applied to any other medical, forensic, or other applications.

[0052] The present disclosure relates to devices, systems and methods that can perform amplification, such as isothermal amplification, of nucleic acids in a sample. When the term amplification is used herein, unless specifically stated otherwise, it is intended to include any variation 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 nucleic acid amplification, but can 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 preparing a sample before testing the sample for the presence or absence of a target of interest.

[0053] Examples of diagnostic testing devices An example diagnostic test device 100 according to the present disclosure will now be described with reference to Figures 1-7E.

[0054] The diagnostic testing device 100 is implemented in a rapid nucleic acid-based testing system capable of performing automated molecular diagnostic tests to detect various analytes of interest. The diagnostic testing device 100 includes a cartridge 106 configured to be inserted into a diagnostic instrument of the testing system. In one non-limiting example, the cartridge 106 is a consumable plastic container. The cartridge 106 can be formed of injection molded plastic or any other suitable material. The cartridge 106 can include a barcode, such as a barcode displayed on an exterior surface of the cartridge 106, which the diagnostic testing device can scan 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 to detect the nucleic acid of interest. A user can input patient and / or sample information via a touch screen on the instrument or barcode scanning.

[0055] As shown in FIG. 1, the diagnostic testing device 100 includes a cartridge 106 as well as a dispensing mechanism 102 configured to interface with the cartridge 106. The cartridge 106 can include a cartridge body 108, a test container 112, and one or more seals 110a and 110b. The diagnostic testing device 100 can include a closure configured to close a first end 120 of the cartridge body 108. For example, the diagnostic testing device can include a dispensing cap 114 and / or a transport cap 116. The dispensing cap 114 can be coupled to the dispensing mechanism 102. The dispensing mechanism 102 can include one or more sealing members 104, such as, for example, an O-ring, a gasket, or a grommet. In the non-limiting embodiment of FIG. 1, the one or more sealing members 104 include two O-rings. As shown in FIGS. 2 and 3, the dispensing cap 114 and the transport cap 116 are each configured to be attached to the first end 120 of the cartridge body 108 to close or seal the first end 120. In one example, the transport cap 116 is configured to reversibly close or seal the first end 120, and the dispensing cap 114 is configured to irreversibly close or seal the first end 120. The cartridge body 108 includes a sample preparation reservoir 202 and one or more cylindrical chambers 206. The cartridge body 108 can form the sample preparation reservoir 108 and one or more cylindrical chambers 206. Substances, such as fluids, present in the sample preparation reservoir 202 and the one or more cylindrical chambers 206 can be enclosed within the cartridge 108. The test container 112 includes one or more diagnostic test reservoirs 204. The test container 112 can form one or more diagnostic test reservoirs 204. Substances, such as fluids, present in the one or more diagnostic test reservoirs 204 can be enclosed within the test container 112.

[0056] The test containers 112 of the cartridge 106 may take any suitable shape and size. In the non-limiting embodiment of Figures 1-7, the test containers 112 include one or more tubes, each tube forming a single diagnostic test reservoir 204. However, it will be understood that other configurations may also be suitably implemented.

[0057] FIG. 4H shows a diagram of the test vessel 112. Amplification of the analytes of interest can occur in one or more diagnostic test reservoirs 204 of the test vessel 112. The one or more diagnostic test reservoirs 204 are physically and fluidically isolated from one another when attached to the cartridge body 106 with the seals 110a and / or 110b. The test vessel 112 can be coupled to a second end 118 of the cartridge body 108 opposite the first end 120. Other configurations can also be suitably implemented. For example, in another non-limiting embodiment, the cartridge body 108 and the test vessel 112 are integrated into a single structure. Amplification, such as, but not limited to, isothermal amplification, and detection, such as, but not limited to, fluorescent detection, of the one or more analytes of interest can be performed in the one or more diagnostic test reservoirs 204. An optical signal can be directed at one or more diagnostic test reservoirs 204, and an optical signal emitted from the one or more diagnostic test reservoirs 204 can be detected and correlated with the presence, and possibly the amount, of one or more analytes of interest. The walls of the test vessel 112 can comprise a plastic, such as, for example, a polypropylene material or any other suitable material (such as, but not limited to, polyethylene). It may be desirable to select a transparent or substantially transparent material such that the optical signal can easily pass through the walls of the test vessel 112.

[0058] It should be understood that the present disclosure is not limited to a test container 112 having two diagnostic test reservoirs 204 as shown in Figures 1 and 4H. For example, the test container 112 can be implemented with one diagnostic test reservoir 204. Alternatively, the test container 112 can be implemented with three, four, five or more diagnostic test reservoirs 204.

[0059] The test container 112 may include a detection tab 432. The detection tab 432 may facilitate detection of the presence or absence of the test container 112 received within the diagnostic test device. For example, the diagnostic test device may include a sensor, such as a mechanical sensor, configured to interact with the detection tab 432 of the test container 112. Upon insertion of the test container 112 into the diagnostic test device, the detection tab 432 may press against the mechanical sensor of the diagnostic test device to indicate that the test container 112 is properly seated within the diagnostic test device. Other configurations may also be suitably implemented. For example, the diagnostic test device may include an optical sensor that emits an optical signal that is intercepted by the detection tab 432 when the test container 112 is properly seated. The detection tab 432 may include a "stepped" shape as shown in FIG. 4H. As described in more detail below, the test container 112 may include a lip 430 that facilitates attachment of the test container 112 to the cartridge body 108.

[0060] The diagnostic test reservoir(s) 204 may be preloaded with reaction components for performing a particular diagnostic test. For example, the diagnostic test reservoir(s) 204 may include lyophilized reagents. The lyophilized reagents may include enzymes, primers, probes, beacons, salts, and / or other reagents used in the assay reaction. Mixed beads may also be included in the diagnostic test reservoir(s) 204. These beads may be magnetic beads. The beads may be embedded within a pellet of lyophilized reagents. The beads may facilitate mixing of the lyophilized reagents with the fluid sample when a fluid sample is introduced into the diagnostic test reservoir(s) 204 to rehydrate the lyophilized reagents. For example, the beads may move under the influence of magnetic forces within the diagnostic test reservoir(s) 204 to create movement within any liquid within the diagnostic test reservoir(s) 204 and aid in dissolving the lyophilized reagents. The beads may include stainless steel or any other suitable material. In another embodiment, liquid reagents may be preloaded into one or more of the diagnostic test reservoirs 204. In such embodiments, it may be further desirable to mix the preloaded liquid reagents with the fluid sample, for example, by agitating magnetic beads contained within the one or more diagnostic test reservoirs 204.

[0061] 4A-4G show an embodiment of a cartridge body 108 according to the present disclosure. As shown in cross-section in 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 underside 410 of the one or more cylindrical chambers 206 is also shown in FIGS. 4A and 4D. The cartridge body 108 may also include a lower surface 424 of the cylindrical chamber 206. The sample preparation reservoir 202 may be preloaded with reaction components for performing a particular diagnostic test. For example, the sample preparation reservoir 202 may be preloaded with a volume of sample preparation fluid. The sample may be carried 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 flushed from the swab into the sample preparation fluid to form 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 recover and / or concentrate nucleic acids, such as DNA and / or RNA. In some embodiments, the sample preparation fluid may include an elution lysis buffer (ELB). As illustrative examples, the ELB may include a blood cell lysis buffer (RBCC), a glycine running buffer solution (GRBS), and / or a sodium dodecylsulfate solution (SDS). In another embodiment, the sample preparation fluid need not be preloaded into the sample preparation reservoir 202, but may be loaded immediately prior to introduction of the sample.

[0062] Figure 4B is a top-down cross-sectional view of the second end 118 of the cartridge body 108, as indicated by the dotted rectangle in Figure 4A. Figure 4C is a side cross-sectional view taken from the dotted line 422 shown in Figure 4A.

[0063] The sample preparation reservoir 202 can have a fluid volume that is several times larger than the one or more diagnostic test reservoirs 204. As an illustrative example, the sample preparation reservoir 202 can have a volume of about 6 mL, while the one or more diagnostic test reservoirs 204 can accommodate a total fluid volume of about 400 μL. In some examples, the sample preparation reservoir 202 can hold a fluid volume of 0-5 mL, 0.5-4.5 mL, 1-4.0 mL, 1.5-3.5 mL, 2-3 mL, or any value or range within or bounded by any of these ranges or values, although values ​​outside of these values ​​or ranges can be used in some cases. Additionally or alternatively, in some examples, the sample preparation reservoir 202 can hold a fluid volume of 1-3 mL. The amount of sample preparation fluid actually held by the sample preparation reservoir 202 can depend on the particular assay.

[0064] 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 example process described below with reference to FIG. 8. The one or more diagnostic test reservoirs 204 can 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, 250 μL of liquid, up to 300 μL of liquid, up to 350 μL of liquid, up to 400 μL of liquid, up to 450 μL of liquid, up to 500 μL of liquid, up to 1000 μL of liquid, or any value or range within or bounded by any of these ranges or values, although values ​​outside of these values ​​or ranges can be used in some instances. Additionally or alternatively, in some instances, the one or more diagnostic test reservoirs 204 can hold a fluid volume of 200 μL.

[0065] In some examples, the cartridge body 108 can include a geometry that facilitates rapid heating of the contents of the sample preparation reservoir 202. For example, the cartridge body 108 can have a relatively high surface area to volume ratio that can facilitate rapid heating, for example, by having an oval cross section. The walls of the cartridge body 108 can include a polypropylene material or any other suitable material (such as, but not limited to, polyethylene). In the embodiment shown in Figures 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 Figures 4D, 4E, and 4G, the angled wall 426 of the cartridge body 108 is a feature that transitions from a circular cross section to an oval cross section. The cross section is relatively circular at the portion of the angled wall 426 closest to the first end 120 and becomes relatively oval as it approaches the cylindrical chamber 206.

[0066] 5A and 5B, dispense cap 114 includes locking tab 502, internal threads 504, overtravel tab 506, plug seal 508, and an inner ring 510 protruding from flange 512. Inner ring 510 in this non-limiting embodiment is a raised annular portion protruding from an inner surface of flange 512. Flange 512 is configured to surround at least a portion of end 606 of dispensing mechanism 102 when dispensing mechanism 102 is coupled to dispense cap 114. Inner ring 510 engages a corresponding ring 610 at end 606 of dispensing mechanism 102 such that dispense cap 114 can freely rotate around dispensing mechanism 102 when dispense cap 114 is coupled to end 606 of dispensing mechanism 102. As described in more detail below, in embodiments of the present disclosure, dispensing cap 114 rotates about the longitudinal axis of dispensing mechanism 102 even though dispensing mechanism 102 remains stationary after insertion into cartridge body 108.

[0067] In this non-limiting example, inner ring 510 and ring 610 are reversibly coupled by a soft interference fit, allowing ring 610 to be reversibly snapped onto and off of inner ring 510. It will be appreciated that other mechanisms for coupling dispensing cap 114 to dispensing mechanism 102 may also be suitably implemented.

[0068] A cap, such as, for example, dispensing cap 114 or shipping cap 116, may engage threaded wall 404 at first end 120 of cartridge body 108. In embodiments of cartridge body 108 including locking threads 412, a cap, such as, for example, dispensing cap 114, may also engage locking threads 412. Twisting locking tab 502 of dispensing cap 114 in a first direction (clockwise in this example) past locking threads 412 locks dispensing cap 114 to first end 120 of cartridge body 108, thereby inhibiting and / or preventing movement of dispensing cap 114 in a second direction opposite the first direction (counterclockwise in this example). FIG. 5D shows locking tab 502 in a locked position against locking threads 412. In the locked position, dispense cap 114 irreversibly engages locking threads 412 such that a user cannot unscrew dispense cap 114 and separate dispense cap 114 from cartridge body 108. An embodiment of cartridge body 108 that includes locking threads 412 has the advantage that the fluid sample can be completely sealed within device 100 when dispense cap 114 engages locking threads 412. This can prevent fluid sample 100 from being unintentionally contaminated or leaking from device 100 during or after a diagnostic test is performed.

[0069] As shown in FIG. 5E, blocking flange 428 of cartridge body 108 can engage over-travel tab 506 of dispense cap 114. Blocking flange 428 can prevent or inhibit dispensing cap 114 from further rotating in a first direction (clockwise in this example) by blocking movement of over-travel tab 506. In some embodiments, engagement of over-travel tab 506 with blocking flange 428 occurs when dispense cap 114 is in substantially the same position as engagement of locking threads 412 with locking tab 502. That is, in some embodiments, each of locking threads 412 and blocking flange 428 can engage locking tab 502 and over-travel tab 506, respectively, such that dispense cap 114 cannot be twisted counterclockwise or clockwise once twisted to the locked position. When engaged, blocking flange 428 and over-travel tab 506 prevent rotational movement of dispense cap 114. When further rotational movement of dispense cap 114 is prevented and / or inhibited, translational movement of dispense cap 102 towards end 410 of cartridge body 108 is also prevented and / or inhibited. Embodiments of the present disclosure have the advantage that translational movement of dispense cap 102 towards end 410 of cartridge body 108 can be stopped at a very precise, predetermined distance from end 410 of the cartridge body, thus ensuring that a precise, predetermined amount of fluid is consistently dispensed from sample preparation reservoir 202 to one or more diagnostic test reservoirs 204. In some non-limiting examples, rotating dispense cap 114 an additional 7-10 degrees in a clockwise direction (beyond the locked position) will result in an additional 10 μL of fluid being dispensed from sample preparation reservoir 202 to one or more diagnostic test reservoirs 204. In some embodiments, the additional 10 μL of dispensed is within 10% error of the dispensed amount. Thus, embodiments of the present disclosure that implement the blocking flange 428 and overtravel tab 506 can consistently deliver precise amounts of fluid to one or more diagnostic test reservoirs 204, thereby increasing the reliability and accuracy of the tests.

[0070] In some embodiments of the present disclosure, the cartridge body 108 includes features that are advantageously arranged to improve the moldability and manufacturability of the cartridge body 108. In one non-limiting example, the protrusion of the cartridge body 108, including the locking threads 412 and the blocking flange 428, extends along less than half the circumference of the upper portion of the cartridge body 108 (e.g., about 170° of the circumference). In some other embodiments, the protrusion can encompass substantially more or less than the circumference of the upper portion of the cartridge body 108, such as 330° of the circumference or 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 can have better moldability. This is because, in such non-limiting examples, the protrusion on which the locking threads 412 and the blocking flange 428 are located does not intersect with the parting line used during manufacturing (e.g., during the injection molding process).

[0071] As shown in FIGS. 5B and 5C, the plug seal 508 of the dispense cap 114 is an annular flange extending from an upper inner surface of the dispense cap 114. The plug seal 508 can engage the first end 120 of the cartridge body 108 when in the locked position. 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 in the cartridge body 108 from flowing or leaking out of the sample preparation reservoir 202 through the first end 120. The plug seal 508 can also prevent and / or inhibit fluid in the sample preparation reservoir from contacting the threaded wall 404 and / or threads 504. Thus, embodiments of the present disclosure implementing the dispense cap 114 with the plug seal 508 can advantageously reduce or eliminate the risk of contamination of the external environment with fluid in the sample preparation reservoir 202 that may contain pathogens.

[0072] In embodiments of the cartridge body 108 that include a key 402, the key 402 can engage with a diagnostic testing device. The key 402 can assist a user in properly orienting the cartridge 106 within the diagnostic testing device. Additionally or alternatively, the diagnostic testing device can sense the key 402 to indicate insertion of the cartridge 106.

[0073] An inner surface or wall 420 near the bottom of the cartridge body 108 can be shaped to define the sides of at least one chamber, such as, for example, a 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. The cartridge body 108 in the illustrated embodiment includes two cylindrical chambers 206, although other embodiments can include one or more cylindrical chambers 206. The cylindrical chambers 206 can include openings 418. Such openings facilitate the dispensing of liquid from the sample preparation reservoir 202 to one or more diagnostic test reservoirs 204. The openings 418 can be covered by a seal 110a. In some embodiments, each opening 418 can be covered by a unique seal 110a such that there is one seal 110a for each opening 418.

[0074] It should be understood that the cartridge body 108 of the present disclosure is not limited to two cylindrical chambers 206 as shown in Figures 1-3, 4A-4G, and 7A-7E. For example, the cartridge body 108 can be implemented with one cylindrical chamber 206. Alternatively, the cartridge body 108 can be implemented with three, four, or five or more cylindrical chambers 206. The number of cylindrical chambers 206 in the cartridge body 108 can correspond to the number of diagnostic test reservoirs 204 in the test container 112.

[0075] The seals 110a and 110b may comprise a foil material, which may be pierced by application of mechanical force. The seals 110a and 110b need not be the same material, but may be in some embodiments. The seal 110b may be attached to the test vessel 112 to cover an opening at the first end 434 of the sample preparation reservoir 202 and separate the sample preparation reservoir 202 from the one or more diagnostic test reservoirs 204. In one non-limiting embodiment, the two seals 110a and 110b are pressed together when the cartridge body 108 and the test vessel 112 are joined into a single cartridge 106. It may be desirable to attach the seal 110b onto the test vessel 112. For example, in some embodiments where the test vessel 112 holds lyophilized reagents, attaching the seal 110b may ensure that moisture and / or other potential contaminants are not introduced into the test vessel 112 prior to joining the test vessel 112 and the cartridge body 108. The presence of moisture and / or contaminants within the test vessel 112 can result in inaccurate assay results, such as false positives or false negatives. When attached to the underside 410 of one or more cylindrical chambers 206, the seal 110a can retain fluids, such as liquid buffers, within the sample preparation reservoir 202 and cylindrical chambers 206. As an illustrative example, the seal 110a can be attached to the underside of the cylindrical chambers 206 by heat welding, and the seal 110b can also be attached to the top of the test vessel 112 by heat welding.

[0076] In some embodiments, only one of the seals 110 may be present. In such embodiments, the seal 110 may be installed to cover the opening 418 of the cylindrical chamber 206 or the first end 434 of the test vessel 112 prior to joining the test vessel 112 and the cartridge body 108. 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 any lyophilized reagents in the diagnostic test reservoir 204 separate from the sample preparation reservoir 202.

[0077] In the exemplary device 100, the cartridge body 108 is coupled to the test reservoir 112 during manufacture 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 reservoir 112. In yet another non-limiting embodiment, the cartridge body 108 and test reservoir 112 are shipped separately to an end user, who couples the cartridge body 108 and test reservoir 112 together prior to operation.

[0078] The cartridge body 108 may be connected to the test container 112 using any number of coupling mechanisms, such as, but not limited to, a lip 406 that matingly connects to a lip 430 on the exterior surface of the test container 112. The sample preparation reservoir 202 and the one or more diagnostic test reservoirs 204 may be joined with a seal 110a and / or 110b therebetween to form the cartridge 106. Thus, the seal 110a may define the bottom of two cylindrical chambers formed by the interior surface 420. The seal 110b may define the top of the two diagnostic test reservoirs 204. Joining the sample preparation reservoir 202 and the one or more diagnostic test reservoirs 204 with the seal 110a therebetween to form a unitary joined structure may be accomplished, for example, by ultrasonic welding, adhesives, snap-fit ​​connections, combinations thereof, or any other suitable joining mechanism. It may be desirable for the sample preparation reservoir 202 and the one or more diagnostic test reservoirs 204 to be joined strongly enough to withstand increased pressure within the cylindrical chamber 206 and / or the one or more diagnostic test reservoirs 204. In embodiments where the sample preparation reservoir 202 and the one or more diagnostic test reservoirs 204 are joined via ultrasonic welding, the test container 112 may include one or more protrusions 438. The one or more protrusions 438 may be spaced along an outer surface of the lip 430. The one or more protrusions 438 may help align the test container 112 against the end 410 and the lip 406 of the second end 118 of the cartridge body 108 during ultrasonic welding. The one or more protrusions 438 may help center the test container 112 relative to the lip 406 of the second end 118 of the cartridge body 108 during ultrasonic welding. For example, the one or more protrusions can ensure that the inspection container 112 is approximately or substantially equidistant from the edge of the lip 406. The one or more protrusions 438 can thereby increase the consistency and / or strength of the ultrasonic weld.

[0079] 5 illustrates a dispense cap 114 that can be coupled to the dispensing mechanism 102, according to an embodiment of the present disclosure. The dispense cap 114 can include threads 504 configured to engage with the threaded wall 404 of the cartridge body 108. In some embodiments, the dispense cap 114 also includes a locking tab 502 that can engage with locking threads 412 of the cartridge body 108. Rotation of the locking tab 502 of the dispense cap 114 past the locking threads 412 can prevent or inhibit further rotation in either direction to lock the dispense cap 114 to the cartridge body 108.

[0080] 6A and 6B show an embodiment of a 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 correspond 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, the sealing members 104, the cylindrical chambers 206, and the diagnostic test reservoirs 204.

[0081] The shaft 604 and the piercing member 602 of the dispensing mechanism 102 can include plastic. The plastic can be, for example, polycarbonate, acrylonitrile butadiene styrene (ABS), nylon, another thermoplastic, polypropylene material, or any other suitable material (such as, but not limited to, polyethylene). The piercing member 602 can include a spike or other relatively sharp feature sufficient to pierce a seal, such as the seal 110a. In one example, the piercing member 602 includes a spike rod. As shown in FIG. 6B, the profile and cross section of the piercing member 602 can be cross-shaped and / or plus sign-shaped. The piercing member 602 can include a chamfered or beveled surface. For example, in the non-limiting embodiment of FIGS. 6A and 6B, the cross section of each piercing member 602 includes a chamfered surface 614. The cross and / or plus sign shapes can facilitate fluid flow over the piercing member 602 and through the piercing seal 110a because fluid can easily flow over the concave surface of the piercing member 602 while the chamfered surface 614 continues to enlarge the opening. The cross or plus sign shape of the piercing member 602 has the advantage that an opening can be formed 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 formed in the seal 110a does not form leaves or sections of seal material that may block or prevent fluid from passing through the opening.

[0082] The cross or plus sign shape of the piercing member 602 also has the advantage of allowing air to exit one or more of the diagnostic test reservoirs 204 and enter the sample preparation reservoir 202 before an opening is fully formed in the seal 110a. For example, air can move over the concave surface of the piercing member 602 while the chamfered surface 614 continues to enlarge the opening. Thus, as the opening is being formed, pressure buildup within the one or more diagnostic test reservoirs 204 that would otherwise act to impede fluid flow into the one or more diagnostic test reservoirs 204 can be countered. This is particularly advantageous in scenarios where the air within the one or more diagnostic test reservoirs 204 is pressurized. It will be appreciated that the advantages of the embodiments of the piercing member 602 discussed above also apply to the formation of an opening in the seal 110b.

[0083] It should be understood that the dispensing mechanism 102 of the present disclosure is not limited to two piercing members 602 as shown in Figures 1 and 6A-7C. For example, the dispensing mechanism 102 can be implemented with one piercing member 602. Alternatively, the dispensing mechanism 102 can be implemented with three, four, or more than four piercing members 602. The number of piercing members 602 of the dispensing mechanism 102 can correspond to the number of cylindrical chambers 206 of the cartridge body 108.

[0084] The dispensing mechanism 102 may include one or more seal members 104, such as, for example, an O-ring, a gasket, or a grommet. The seal member 104 may surround at least a portion of the piercing member 602. FIGS. 6A and 6B show an embodiment in which the seal member 104 is an O-ring. FIGS. 6C-6F show another embodiment in which the seal member 104 is one or more gaskets. FIGS. 6E and 6F show top and bottom views of another embodiment of the seal member 104. In some embodiments in which the seal member 104 is a gasket as shown in FIG. 6D, the seal member may be formed separately from the dispensing mechanism 102 and coupled to the dispensing mechanism 102 by forcing the gasket seal member 104 over the piercing member 602. In some embodiments, the gasket seal member 104 may be overmolded onto 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.

[0085] In one example where the piercing member 602 includes a spike rod, the seal member includes a seal member 104 that surrounds the spike rod. The seal member 104 can be configured to directly contact the inner surface 420. In an embodiment where the seal member 104 includes two O-rings, substantially the entire circumference of each O-ring can directly contact the inner surface 420 of the cylindrical chamber 206 of the cartridge body 108. In some cases, such as the non-limiting example shown in Figures 6A and 6B, each O-ring includes two annular portions spaced a distance apart. Substantially the entire circumference of each annular portion 612 can directly contact the inner surface 420 of the cylindrical chamber 206 of the cartridge body 108. In such cases, the presence of two separate annular portions can form a two-part seal against the inner surface 420 and 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 directly contacts the inner surface 420 of the cylindrical chamber 206 of the cartridge body 108. In such embodiments, the presence of two separate annular portions 612 spaced a distance apart forms a two-part seal against the inner surface 420 and can provide redundancy in the event that one annular portion 612 does not form an effective seal against the inner surface 420.

[0086] The seal member 104 can include an elastomeric material suitable for forming a liquid-tight or substantially liquid-tight seal when pressed against the material of the cartridge body 108. In some cases, the seal member 104 includes a compressible material. In some non-limiting examples, the seal member 104 includes rubber, butyl rubber, thermoplastic vulcanizate (TPV), and / or thermoplastic elastomer (TPE). In some embodiments in which the seal member 104 is an O-ring, the seal member 104 can include 70 Shore A butyl rubber, for example. In some 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 can include 60 Shore A TPV. It will be understood that many other materials can also be suitably implemented in accordance with the present disclosure. The dispense cap 114 can be coupled to the dispensing mechanism 102. For example, dispensing cap 114 can be coupled to dispensing mechanism 102 such that it can rotate about a longitudinal axis of dispensing mechanism 102. In one non-limiting embodiment, end 606 of dispensing mechanism 102 engages inner ring 510 on the inner top surface of dispensing cap 114 using a snap-fit ​​mechanism that allows dispensing mechanism 102 to rotate freely relative to dispensing cap 114.

[0087] 4B and 4C, in embodiments having two or more cylindrical chambers 206, there can be a portion 414 of the interior surface separating two cylindrical chambers 206. The portion 414 of the interior surface between the two cylindrical chambers 206 can be formed to include a negative space, such as, for example, a notch 416. The notch 416 can at least partially define the predetermined amount of fluid dispensed from the sample preparation reservoir 202 to the one or more diagnostic test reservoirs 204. Thus, the depth of the notch 416 can be altered to adjust the predetermined amount dispensed from the sample preparation reservoir 202 to the one or more diagnostic test reservoirs 204.

[0088] The predetermined volume of fluid dispensed into one or more diagnostic test reservoirs 204 is determined by at least three variables: the radius of the cylindrical chamber 206, the height H of the cylindrical chamber 206 measured between the lower surface 424 and the lowest point of the notch, and the amount displaced by the piercing member 602. The depth of the notch 416, illustrated by distance D in FIG. 4C, affects the height H at which the one or more seal members 104 engage the inner surface between the two cylindrical chambers 206, and therefore the depth of the notch 416 is inversely related to the predetermined volume dispensed. Below, three non-limiting examples are described that illustrate the effect of the notch 416 on the predetermined volume of fluid dispensed. In these three examples, the only dimensional change associated with the predetermined volume of fluid dispensed is the dimensional change to the depth D of the notch 416.

[0089] In a first non-limiting example shown in Figures 4B and 4C, the depth D of the notch 416 is about 0.2 mm for an embodiment in which a volume of fluid of about 100 μL is dispensed from each cylindrical chamber 206 to a corresponding diagnostic test reservoir 204. In a second non-limiting example, the depth D of the notch 416 is about 0.1 mm, and a volume of fluid of more than about 100 μL is dispensed from each cylindrical chamber 206 to a corresponding diagnostic test reservoir 204. This is because the depth D of the notch 416 in this second non-limiting example is less 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 of the first example, resulting in a larger volume of fluid contained within the chamber. In a third non-limiting example, the depth D of the notch 416 is about 0.4 mm, and less than about 100 μL of fluid is dispensed into the one or more diagnostic test reservoirs 204. This is because the depth D of the notch 416 in this 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, resulting in a smaller amount of fluid contained within the chamber. In some embodiments, the depth D of the notch 416 is about 0 mm to 2 mm, about 0 mm to 1.5 mm, about 0 mm to 1 mm, or about 0.1 mm to 0.4 mm, although other values ​​or ranges may be used in some instances. In a 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.

[0090] In embodiments in which the dispensing mechanism 102 includes two or more piercing members 602, the dispensing mechanism 102 may include a slot 608. The slot 608 is a void in the dispensing mechanism 102. The slot 608 may allow the one or more piercing members 602 and the one or more sealing members 104 to pass over a portion 414 of the inner surface between the two cylindrical chambers 206.

[0091] 7A-7E show four different positions of a dispensing mechanism 102 within a sample preparation reservoir 202 during a dispensing operation according to the present disclosure, which involves movement of the dispensing mechanism 102 relative to the cartridge body 108 to break seal 110a and / or seal 110b to 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 directly contact the inner surfaces that define the sides of the sample preparation reservoir 202 as the dispensing mechanism 102 translates along the longitudinal axis 108.

[0092] 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 can be manually placed in this position by inserting the dispensing mechanism into the cartridge body 108 from above. The seals 110a and 110b are intact. As described above, the dispensing mechanism 102 can be coupled to the dispensing cap 114. The dispensing cap 114 is configured to engage the threaded wall 404 of the sample preparation reservoir 202. The seal member 104 is located above the cylindrical chamber 206 and thus is not yet engaged with the cylindrical chamber 206. However, because the sample preparation reservoir 202 is wider than it is deep (i.e., the top-down cross-section of the sample preparation reservoir 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 if the piercing member 602 is located higher than the cylindrical chamber 206 within the cartridge body 108.

[0093] 7B shows the dispensing mechanism 102 after piercing seal 110a and / or seal 110b. After engaging threaded wall 404 with dispensing cap 114 and continuing to twist dispensing cap 114, dispensing mechanism 102 may be in the position shown in FIG. 7B relative to the position shown in FIG. 7A. As described above, dispensing cap 114 is coupled to an upper end 606 of shaft 604 of dispensing mechanism 102. This coupling allows for free rotation of dispensing cap 114 relative to shaft 604 and piercing member 602. Thus, the interaction of threaded wall 404 and threads 504 translates the twisting of dispensing cap 114 into vertical translational motion of dispensing mechanism 102 along longitudinal axis 108. As cap 114 is twisted clockwise relative to cartridge body 108, dispensing mechanism 102 translates downward. In this position, dispensing cap 114 has not yet engaged locking tab 502 and can continue to rotate relative to dispensing mechanism 102 and cartridge body 108.

[0094] 7B, dispensing mechanism 102 includes two seal members 104 and two piercing members 602 configured to interact with two cylindrical chambers 206 formed by inner surfaces 420. Threading and twisting dispensing cap 114 onto cartridge body 108 translates dispensing mechanism 102 downwards, thus causing the piercing members to approach and breach seals 110a and 110b. This translation forces piercing member 602 to penetrate seal 110a.

[0095] As the dispensing mechanism 102 translates downward, the air in the diagnostic test reservoirs 204 is compressed, so pressure can increase in the one or more diagnostic test reservoirs 204 below the one or more seal members 104. The threaded wall 404 and threads 504 can be configured to withstand the upward force of this pressure increase. When the dispensing cap 114 locks with the locking threads 412, the interaction between the locking threads 412 and the dispensing cap 114 can likewise withstand upward movement. The bond between the test container 112 and the cartridge body 108 must also be strong enough not to be broken by this pressure increase.

[0096] 7C shows the dispensing mechanism 102 and cartridge body 108 immediately after the piercing member 602 has pierced the seal 110a, but before any fluid has been transferred 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, such that each seal member 104 forms a complete seal with the inner surface 420 of the cylindrical chamber 206 to prevent or substantially prevent fluid from flowing relative to the seal member 104, i.e., 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 downwardly below the seal member 104. The lowest point of the notch 416 defines the height at which the upper surface of the cylindrical chamber 206 can be defined, and thus the 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 translates further downward, seal member 104 and piercing member 602 force the predetermined volume to flow through the pierced seal 110a and into diagnostic test reservoir 204.

[0097] As shown in Figures 7D and 7E, the entire dispense mechanism 102 translates downward relative to the cartridge body 108 until the predetermined volume, shown as a shaded area at the bottom of the diagnostic test reservoir 204 in Figure 7E, has been completely and / or substantially dispensed into the diagnostic test reservoir 204. In some embodiments, some fluid may remain in the cylindrical chamber 206 when the dispense cap 114 locks. In some embodiments, the seal member 104 may snugly contact the lower surface 424 of the cylindrical chamber 206 once the predetermined volume has been dispensed into the diagnostic test reservoir 204. In some embodiments, the seal member 104 directly contacts the lower surface 424 of the cylindrical chamber 206 once the predetermined volume has been dispensed into the diagnostic test reservoir 204. The dispense cap 114 is configured to lock against the locking threads 412 and blocking flange 428 when the end of the predetermined volume has been dispensed from the one or more cylindrical chambers 206. As a result, rotation of the dispense cap 114 relative to the cartridge body 108 and shaft 604 is inhibited and / or prevented, thereby preventing further and / or reverse translational motion of the dispense mechanism 102 relative to the cartridge body 108. These and other features can enable embodiments of a diagnostic test reservoir 100 according to the present disclosure to accurately and consistently dispense no less than or no more than a predetermined amount of fluid into the diagnostic test reservoir.

[0098] Because the piercing member 602 and the sealing member 104 are locked in place as described above, the predetermined volume dispensed into the one or more diagnostic test reservoirs 204 is also locked within the test container 112. The piercing member 602 and the sealing member 104 prevent the predetermined volume of fluid from moving out of the diagnostic test reservoir 204. Also, because the piercing member 602 and the sealing member 104 are locked in place, no additional fluid or other potential contaminants outside 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 locked within the one or more diagnostic test reservoirs can be subjected to processing, such as, for example, thermal and / or optical processing. Such processing can serve to generate a result indicative of the presence or absence of one or more target analytes within a sample introduced to the diagnostic test device 100.

[0099] Sample Processing with Diagnostic Test Devices FIG. 8 illustrates an example process for using a diagnostic device 100 according to the present disclosure. This process can be performed using the exemplary embodiments as shown in 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 a user to remove the transport cap 116 from the cartridge body 108. At block 802, a swab is inserted into the sample preparation reservoir 202 of the cartridge body 108 to deposit a sample. The instructions may instruct a user to swirl the tip of the swab within the sample preparation reservoir 202 according to a predetermined protocol, such as, for example, a certain number of rotations and / or a certain duration.

[0100] It will be appreciated that the sample can be dispensed into the sample preparation reservoir 202 using any suitable method. For example, the sample can be dispensed directly into the sample preparation reservoir 202 without the use of a swab (such as 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 any suitable sample can be added to the sample preparation reservoir 202, including solid or gas samples.

[0101] In this embodiment, the swab is then removed from the sample preparation reservoir 202 and discarded. The shipping cap 116 can then be screwed back onto the cartridge body 108. In another example, the shipping cap 116 is not screwed back onto the cartridge body 108.

[0102] The process then proceeds 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. If the cartridge 106 is oriented such that the end 120 including the threaded wall 404 faces up (i.e., the cartridge 106 is not upside down), the fluid sample can pool without air bubbles within the cylindrical chamber 206 of the sample preparation reservoir 202 under the influence of gravity. After mixing, it may be desirable for the fluid sample to pool without air bubbles within the cylindrical chamber 206 so that an intended amount of fluid can be dispensed into the sample preparation reservoir 202. In embodiments where the transport cap 116 is not re-engaged to the cartridge body 108, block 804 may include mixing the fluid sample without inverting the cartridge body 108.

[0103] In some examples, the sample preparation fluid can be heated prior to introducing the swab into the sample preparation fluid and mixing the sample. In other examples, the sample preparation fluid is heated after mixing with the sample. In embodiments where the sample is added directly to the sample preparation reservoir 202, the sample can be added before or after the sample preparation solution is heated. If particles containing the analyte of interest are present in the sample, the particles can be dissolved in solution by chemical action and / or an increase in temperature of the sample preparation solution.

[0104] The process then proceeds to block 806, where the cartridge 106 is inserted into the diagnostic testing instrument. The sample in the sample preparation fluid is then processed. If a shipping cap 116 is present, it may be removed before or after the cartridge 106 is placed into the diagnostic testing instrument. The shipping cap 116 does not include a locking tab that engages with the locking threads 412 of the cartridge body 108, and therefore cannot be locked to the cartridge body 108 like the dispensing cap 114.

[0105] The process then proceeds to block 808 with inserting the dispensing mechanism 102 into the sample preparation reservoir 202. The dispensing mechanism 102 is lowered vertically through the sample preparation reservoir 202 toward the seal 110a such that each piercing member 602 and sealing member 104 is aligned or substantially aligned with a corresponding cylindrical chamber 206. As the dispensing mechanism 102 is lowered within the sample preparation reservoir 202, fluid is able to flow around and over the dispensing mechanism 102.

[0106] The process then proceeds to block 810 where the dispensing cap 114 of the dispensing mechanism 102 engages the sample preparation reservoir 202 , in this example, the threaded wall 404 of the sample preparation reservoir 202 .

[0107] Once the dispensing cap 114 has descended a certain distance down the threaded wall 404, the dispensing mechanism 102 is in 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 comes above the seal 110a, thereby separating the sample preparation reservoir 202 from the one or more diagnostic test reservoirs 204. The inner surface 420, the seal 110a, the seal member 104, and the piercing member 602 cooperate to 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 encapsulates the predetermined volume of fluid by forming a fluid seal with the inner surface 420. Once the seal member 104 engages the inner surface 420 , fluid present within the sample preparation reservoir 202 above the seal member 104 cannot enter the two cylindrical chambers 206 .

[0108] In some examples, the predetermined amount of fluid sealed within each cylindrical chamber 206 can be 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 or range within or bounded by any of these ranges or values, although values ​​outside of these values ​​or ranges can be used in some cases. Additionally or alternatively, in some examples, the predetermined amount of fluid is about 100 μL of liquid.

[0109] The dispensing cap 114 is then further rotated to translate 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 the one or more diagnostic test reservoirs 204. With further translation, the seal member 104 acts as a piston sliding along the inner surface 420 of the sample preparation reservoir 202 to form a sliding seal between the two cylindrical chambers 206 of the sample preparation reservoir 202. For example, the seal member 104 and the inner surface 420 come into intimate contact within the two cylindrical chambers 206 of the sample preparation reservoir 202, resulting in a fluid-tight seal between the seal member 104 and the inner surface 420.

[0110] The method then proceeds to block 812 and pierces the seals 110a, 110b to allow a predetermined amount of fluid from within the cylindrical chamber 206 to flow into the diagnostic test reservoir 204 by the downward movement of the dispense mechanism 102. This dispense action forces a predetermined amount of fluid into the diagnostic test reservoir 204. The seals 110a, 110b ensure that there is no fluid communication between the sample preparation reservoir 202 and the one or more diagnostic test reservoirs 204 until the dispense action. When the seal member 104 forms a seal with the inner surface 420, fluid in the sample preparation reservoir above the seal member 104 is prevented from being dispensed into the one or more diagnostic test reservoirs 204. Thus, in embodiments of the disclosed systems and methods, a first portion of the total fluid volume present in the sample preparation reservoir 202 is dispensed into the diagnostic test reservoir 204 while a second portion of the total fluid volume present in the sample preparation reservoir 202 is not dispensed into the diagnostic test reservoir 204. In some embodiments where there are two cylindrical chambers 206 each capable of dispensing about 100 μL, there can be 500 μL or more of fluid in the sample preparation reservoir. In some embodiments where there are two cylindrical chambers 206 each capable of dispensing about 100 μL, there can be 1-3 mL of fluid in the sample preparation reservoir 202. In some embodiments, the total fluid volume present in the sample preparation reservoir 202 is 1-300 times greater than the volume of the predetermined volume dispensed into the diagnostic test reservoir 204. In some embodiments, the total fluid volume present in the sample preparation reservoir 202 is 5-50 times greater than the volume of the predetermined volume dispensed into the diagnostic test reservoir 204. Ensuring that a consistent volume of fluid is dispensed into the diagnostic test reservoir 204 can reduce variability in assay results. Ensuring that the volume of fluid is consistently dispersed to the bottom of the diagnostic test reservoir can also ensure a high likelihood that sufficient sample material, such as genomic material, is available for the assay reaction to ensure accurate test results.

[0111] In this non-limiting example of the disclosure, one or more diagnostic test reservoirs 204 include two receiving chambers that cooperate to form the 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 perform an amplification reaction in the fluid dispensed into the diagnostic test reservoir 204. An optical fluorescent signal from the diagnostic test reservoir 204 can be detected through the wall of the test vessel 112.

[0112] As described in further detail below, in a non-limiting embodiment of the present disclosure, the dispensing mechanism 102 is free to move along the longitudinal axis of the sample preparation reservoir 202 to the point where the locking tabs engage the locking threads. Fluid within the sample preparation reservoir 202 flows relative to the dispensing mechanism 102 as the dispensing mechanism 102 moves down 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 components of the diagnostic testing device 100 that can move during operation by a user. The entire dispensing mechanism 102 translates downward along the longitudinal axis of the diagnostic testing reservoir 204 in a single motion until translation of the entire dispensing mechanism 102 is prevented as described above. The downward movement of the dispensing mechanism 102 first defines a predetermined volume of fluid surrounded 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 seals 110a, 110b to be pierced by the piercing member 602. Further downward movement of the dispensing mechanism 102 ultimately dispenses a predetermined volume of the fluid sample into the diagnostic test reservoir 204 through the piston action of the dispensing mechanism and the seal formed by the sealing member 104. This results in the dispensing of a single predetermined volume of the fluid sample into a single diagnostic test reservoir 204.

[0113] Concurrent with the downward movement of the dispense mechanism 102 along the longitudinal axis of the sample preparation reservoir 202, the dispense cap 114 rotates about the longitudinal axis of the sample preparation reservoir 202, causing the locking threads 412 of the cartridge 106 to engage the locking tabs 502 of the dispense cap 114. The locking tabs 502 on the dispense cap 114 rotate past the end of the locking threads 412 during the final rotation of the cap 114 which causes the piercing member 602 to pierce the seals 110a, 110b. As a result, the locking threads 412 substantially prevent and / or inhibit rotational movement of the dispense cap 114 in either direction, and also substantially prevent and / or inhibit translational movement of the dispense mechanism 102. It may be desirable for the locking threads 412 to lock onto the top of the cartridge 106 such that the fluid in the test preparation reservoir 202 remains sealed during and after the test operation. Additionally, embodiments of this locking mechanism according to the present disclosure can advantageously lock the dispensing mechanism 102 in place to prevent further movement of liquids and / or reagents between the sample preparation reservoir 202 and the diagnostic test reservoir 204.

[0114] In the devices, systems, and methods according to the present disclosure, the dispensing mechanism 102 is a monolithic, one-piece structure that is the only moving component within the sample preparation reservoir 202, reducing the possibility of alignment errors during sealing by the seal member 104 and dispensing fluid into the diagnostic test reservoir 204. In embodiments of the present disclosure, the seal member 104 is easily aligned and securely seated within the two cylindrical chambers 206. There is a single stroke movement that causes the dispense mechanism 102 to translate downward, resulting in a dispense operation. Consistent and secure sealing of the seal member 104 during a dispense operation has the advantage of contributing to a consistent and accurate partial volume of fluid within the sample preparation reservoir 202 being dispensed into the diagnostic test reservoir 204. This can advantageously contribute to more consistent and accurate testing for the presence or amount of an analyte of interest within the fluid dispensed into the diagnostic test reservoir 204.

[0115] The method then proceeds to block 814, where if a lyophilized reagent is present in the diagnostic test reservoir 204, a predetermined amount of fluid dispensed into the diagnostic test reservoir 204 may rehydrate the lyophilized reagent. The combination of the predetermined amount of fluid in the diagnostic test reservoir 204 and the rehydration reagent is referred to herein as an amplification fluid. It will be understood that embodiments of the present disclosure are not limited to using the dispensed fluid to rehydrate reagents or to providing reagents 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 in the diagnostic test reservoir 204 that is being tested for the presence or amount of an analyte of interest.

[0116] Once the reagents are rehydrated, the method proceeds to block 816 and performs a reaction in the amplification fluid in the diagnostic test reservoir 204. The reaction can include an amplification reaction. The reaction can include an assay. The reaction involves applying heat to the diagnostic test reservoir 204, which is transferred to the fluid to drive an isothermal amplification reaction. In other cases, the amplification reaction involves cyclic heating to perform the amplification reaction. It will be understood that these exemplary reactions and assays are not limiting and any suitable reaction can be performed in the fluid in the diagnostic test reservoir 204.

[0117] The method ends at block 818 with detecting the presence or absence of the analyte of interest. The analyte of interest can 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 of the analyte can be detected, for example, via a fluorescent signal generated during the amplification reaction.

[0118] Methods for using diagnostic testing devices with diagnostic testing equipment In some examples, the diagnostic testing device 100 may be introduced into the diagnostic testing instrument 900 before or after a dispensing operation as described herein has been performed. The device may be inserted into one or more heat blocks 902, 904 of the diagnostic testing instrument 900 that are 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 instrument 900.

[0119] In one non-limiting embodiment, the diagnostic testing device 900 applies heat to the amplification fluid in the diagnostic testing reservoir 204 using a heat block 902 to perform an amplification reaction. The diagnostic testing device 900 also directs optical signals to and receives optical signals from the diagnostic testing reservoir 204 to detect the presence, if any, of an analyte of interest in the amplification fluid in the diagnostic testing reservoir 204. The diagnostic testing device 900 can use one or more image sensors (not shown) to optically scan a portion of the test container 112, such as the bottom 436 of the test container 112. Such scanning can be used to detect and / or measure a positive control reporter in the amplification fluid. Measuring the positive control reporter can ensure that the dispense operation and amplification reaction can continue as intended. Such scanning can also be used to detect and / or measure the progress of the test assay reaction. For example, the diagnostic test device 900 may optically scan the bottom of the diagnostic test reservoir 204 to detect and / or measure changes in fluorescence indicative of an ongoing amplification reaction due to the presence of analyte. As noted above, embodiments of the present disclosure are not limited to real-time detection during the reaction, and in some cases detection is performed upon completion of the reaction.

[0120] 9 is a cross-sectional view of a diagnostic testing device 100 received within one or more heat blocks 902, 904 of a diagnostic testing instrument 900. The diagnostic testing device 100 includes a dispensing mechanism 102 received within a sample preparation reservoir 202. In this non-limiting example, a test container 112 is received within a first heat block 902 of the diagnostic testing instrument 900, and the sample preparation reservoir 202 is received within a second heat block 904 of the diagnostic testing instrument 900. The second heat block 904 can apply heat to the cartridge body 108 to facilitate preparation of a sample for an assay or reaction in fluid within the sample preparation reservoir of the cartridge body 108. Heating the cartridge body 108 can also heat the fluid contained within the sample preparation reservoir 202. The heat block 902 can apply heat to the test vessel 112 after a partial fluid volume in the sample preparation reservoir 202 has been dispensed into the test vessel 112 to carry out an amplification reaction in the amplification fluid present in the test vessel 112. A window in the heat block 902 (not shown in this cross-sectional view) can direct optical signals to and receive optical signals from the one or more diagnostic test reservoirs 204 to enable detection of the presence of an analyte of interest in the amplification fluid, if any.

[0121] One or more optical sensors incorporated within the diagnostic test device 900 can capture fluorescent signals emitted from the amplification fluid during or after the amplification reaction. The digital output from the one or more image sensors can be used to verify the progress of the test assay and the correct release and flow of test reagents within the cartridge, thus allowing the controller to verify the integrity of the test and use this integrity to increase the confidence and accuracy of the test results.

[0122] 10-61 show another non-limiting implementation of a diagnostic test device according to the present disclosure. FIGS. 10-18 are perspective, front, rear, left, right, top, bottom, top exploded, and bottom exploded views, respectively, of a diagnostic test device including a dispensing cap. FIGS. 19-27 are perspective, front, rear, left, right, top, bottom, top exploded, and bottom exploded views, respectively, of a diagnostic test device including a transport cap. FIGS. 28-34 are perspective, front, rear, left, right, top, and bottom views, respectively, of a dispensing cap of a diagnostic test device. FIG. 35 is a cross-sectional view taken along line 35-35 of FIG. 33. FIG. 36 is a cross-sectional view taken along line 36-36 of FIG. 33. 37-43 are perspective, front, rear, left, right, top, and bottom views, respectively, of a piercing member of a diagnostic test device. FIG. 44 is a cross-sectional view taken along line 44-44 of FIG. 42. FIGS. 45-51 are perspective, front, rear, left, right, top, and bottom views, respectively, of a cartridge body of a diagnostic test device. FIG. 52 is a cross-sectional view taken along line 52-52 of FIG. 50. FIG. 53 is a cross-sectional view taken along line 53-53 of FIG. 50. FIGS. 54-60 are perspective, front, rear, left, right, top, and bottom views, respectively, of a test container of a diagnostic test device. FIG. 61 is a cross-sectional view taken along line 61-61 of FIG. 54.

[0123] The operation of a diagnostic testing device that is manually operated and visually read, without the use of an instrument In some applications, the diagnostic testing device 100 can be used manually without a meter. For example, in some embodiments, the diagnostic testing device 100 is held in one hand while the other hand removes the transport cap 116, adds sample, inserts the dispensing mechanism 102 into the cartridge body 108, and attaches the dispensing cap 114 to the cartridge body 108 and rotates it closed. In some such embodiments where the diagnostic test reservoir(s) 204 are visually transparent, the dispensing of fluid into the diagnostic test reservoir(s) 204 can be visually observed and a change in color or turbidity observed over a period of time to provide a diagnostic test readout or indication. This approach takes advantage of operating with a cartridge 106 that is fully sealed once sample is added and internally dispenses a measured amount of prepared sample fluid into the diagnostic test reservoir(s) 204 without the use of an external fluid transfer step.

[0124] Optionally, a stand may be provided to support the diagnostic test device 100 for removing the transport cap 116, adding sample, inserting the dispensing mechanism 102, and attaching, closing and locking the dispensing cap 114 onto the cartridge body 108.

[0125] 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 device 100, while the diagnostic test device 100 is manually withdrawn to observe the test results visible in one or more of the diagnostic test reservoirs 204. In some applications, the heater block may include a window through which the diagnostic test reservoir(s) 204 may be viewed. In such applications, it is not necessary to withdraw the diagnostic test device 100 from the heating block to observe the test results.

[0126] term Conjunctional expressions such as "at least one of X, Y, and Z," unless otherwise indicated, are generally understood in conjunction with the context to be used to convey that an item, term, etc. may be either X, Y, or Z. Thus, such conjunctive expressions generally do not imply that the presence of at least one of X, at least one of Y, and at least one of Z is required in some embodiments.

[0127] As used herein, expressions of degree such as "approximately," "about," "generally," and "substantially" refer to a value, amount, or characteristic that is close to the recited value, amount, or characteristic that still results in performing a desired function or obtaining a desired result. For example, the terms "approximately," "about," "generally," and "substantially" can refer to an amount that is less than 10%, less than 5%, less than 1%, less than 0.1%, and less than 0.01% of the recited amount.

[0128] The term "and / or" as used herein has its broadest, most open-ended meaning that the disclosure includes A only, B only, both A and B, or either A or B, but does not require both A and B, or requires one of A or one of B. As used herein, the phrases A, B "and" and C "at least one of" should be construed to mean the logical A or B or C, using a non-exclusive logical or.

[0129] As used herein, conditional language, such as "can, could, might, may," among others, is generally intended to convey that some features, elements, and / or steps are optional, unless specifically indicated otherwise or understood otherwise within the context of use. Thus, such conditional language is generally not intended to imply that features, elements, and / or steps are required at all. Terms such as "comprising, including, having," and the like, are used in an inclusive, open-ended manner and do not exclude additional elements, features, acts, operations, etc. Additionally, the term "or" is used in an inclusive (rather than exclusive) sense, e.g., when used to connect a list of elements, it means one, some, or all of the elements in the list.

[0130] The methods disclosed herein do not have to be performed in any order as described. The methods disclosed herein include certain actions performed by a practitioner, but may also include third-party direction of those actions, either explicitly or implicitly.

[0131] Some or all of the methods and tasks described herein can be performed by a computer system and fully automated. A diagnostic testing system according to the present disclosure can include a computer system including multiple different computers or computing devices (e.g., physical servers, workstations, storage arrays, cloud computing resources, etc.) that can communicate and interoperate over a network to perform the described functions in some cases. Typically, each such computing device includes a processor (or multiple processors) that executes program 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 can be embodied in such program instructions and / or implemented in the application-specific circuitry (e.g., ASIC or FPGA) of the computer system. When a computer system includes multiple computing devices, these devices can be, but are not required to be, co-located. Results of the disclosed methods and tasks can be persistently stored by transforming physical storage devices, such as fixed memory chips and / or magnetic disks, into different states. The computer system can be a cloud-based computer system whose processing resources are shared by multiple different business entities or other users.

[0132] Although novel features have been illustrated, described, and pointed out in the above detailed description, it will be understood that various omissions, substitutions, and changes in form and details of the devices, systems, and methods may be made without departing from the spirit of the invention. As will be appreciated, some features may be used or practiced separately from other features, and therefore some portions of the specification may be embodied in a form that does not provide all of the features and advantages set forth herein. Thus, the disclosure is not limited to the specific embodiments disclosed herein, but is intended to cover all modifications and alternatives that fall within the true scope and spirit of the disclosure.

Claims

1. A device, a sample preparation reservoir configured to receive a sample at a first end and including an inner surface at a second end defining at least one chamber; at least one diagnostic test reservoir; at least one seal disposed between the sample preparation reservoir and the at least one diagnostic test reservoir; a dispensing mechanism configured to be inserted into the first end of the sample preparation reservoir and to translate toward the second end of the sample preparation reservoir; Equipped with the dispensing mechanism includes a piercing member and a sealing member; the seal member is configured to engage the side of the at least one chamber when the dispensing mechanism translates toward the second end of the sample preparation reservoir; when the seal member engages the side of the at least one chamber, a predetermined volume of fluid is defined between the seal member, the piercing member, the side of the at least one chamber at the second end of the sample preparation reservoir, and the at least one seal; the piercing member is configured to pierce the at least one seal after the predetermined amount has been determined; the seal member and the piercing member are configured to dispense the determined volume from the sample preparation reservoir to the at least one diagnostic test reservoir after the seal is pierced. device.

2. the seal member is configured to directly contact the interior surface defining the side of the at least one chamber when the dispensing mechanism translates toward the second end of the sample preparation reservoir. The device of claim 1 .

3. the piercing member does not move relative to the sealing member when the determined volume is dispensed into the at least one diagnostic test reservoir. The device of claim 1 .

4. The piercing member includes at least one spike rod, and the sealing member includes at least one gasket surrounding the at least one spike rod. The device of claim 1 .

5. a single action of translating the dispensing mechanism toward the second end of the sample preparation reservoir (a) defines the predetermined volume of fluid between the sealing member, the piercing member, the side of the at least one chamber, and the at least one seal; (b) pierces the at least one seal; and (c) dispenses the defined volume into the at least one diagnostic test reservoir. The device of claim 1 .

6. the sample preparation reservoir, the at least one diagnostic test reservoir, and the at least one seal are connected to form a joint structure; The device of claim 1 .

7. the interior surface at the second end of the sample preparation reservoir defines at least one cylindrical chamber; The device of claim 1 .

8. the interior surface at the second end of the sample preparation reservoir defines at least two cylindrical chambers; The device of claim 7.

9. further comprising a notch in a portion of the interior surface between the two cylindrical chambers, the predetermined amount being determined at least in part by a depth of the notch. The device of claim 8.

10. the seal member is configured to directly contact a lower interior surface of the at least one chamber when the determined volume has been dispensed from the sample preparation reservoir into the at least one diagnostic test reservoir. The device of claim 1 .

11. the interior surface at the second end of the sample preparation reservoir defines two cylindrical chambers; each of the two cylindrical chambers configured to dispense the predetermined volume of fluid; the piercing member includes two spike rods; the sealing member includes a gasket surrounding each of the two spike rods; the device further comprises a test container containing two diagnostic test reservoirs; each diagnostic test reservoir configured to receive said predetermined volume of fluid from one of said two cylindrical chambers; The device of claim 1 .

12. the interior surface at the second end of the sample preparation reservoir defines four cylindrical chambers; the device comprises four diagnostic test reservoirs; The device of claim 1 .

13. the sealing member comprises an elastomeric material; The device of claim 1 .

14. the piercing member includes one or more spikes; The device of claim 1 .

15. each of the one or more spikes includes a cruciform cross-section including a concave surface and a chamfered surface; 15. The device of claim 14.

16. the sample preparation reservoir contains a sample preparation fluid; The device of claim 1 .

17. the at least one seal includes a first seal configured to seal the second end of the sample preparation reservoir and a second seal configured to seal the diagnostic test reservoir. The device of claim 1 .

18. the at least one seal comprises a foil; The device of claim 1 .

19. the sample preparation reservoir is configured to receive a swab containing the sample; The device of claim 1 .

20. the second end of the sample preparation reservoir includes a lip configured to be joined to the diagnostic test reservoir. The device of claim 1 .

21. the sample preparation reservoir is configured to contain a volume of fluid in the range of 1 to 3 mL, and the predetermined volume is in the range of 10 μL to 1 mL; The device of claim 1 .

22. the sample preparation reservoir is configured to contain a fluid volume that is 1 to 300 times greater than the predetermined volume; The device of claim 1 .

23. the sample preparation reservoir is configured to contain a fluid volume of 1-3 mL, and the predetermined volume is approximately 100 μL; The device of claim 1 .

24. the dispensing mechanism includes a cap configured to engage the first end of the sample preparation reservoir; The device of claim 1 .

25. the cap is configured to rotate relative to the piercing member; 25. The device of claim 24.

26. the first end of the sample preparation reservoir includes threads configured to engage threads on the cap; 25. The device of claim 24.

27. the cap is configured to lock onto the first end of the sample preparation reservoir to prevent substantial movement of the cap relative to the sample preparation reservoir; the cap includes a plug seal configured to engage an upper end of the sample preparation reservoir; the plug seal is configured to prevent fluid flow when engaged with the top end of the sample preparation reservoir; 25. The device of claim 24.

28. configured to receive the device of claim 1; Diagnostic testing equipment.

Images