Test cartridge with integrated transport module

Abstract

A system is described herein according to an embodiment, which includes a cartridge housing and a hollow transfer module. The cartridge housing further includes at least one sample inlet, a plurality of storage chambers, a plurality of reaction chambers, and a fluidic network. The fluidic network is designed to connect the at least one sample inlet, a portion of the plurality of storage chambers, and a portion of the plurality of reaction chambers to a plurality of first ports, which are located on an inner surface of the cartridge housing. The hollow transfer module includes a plurality of second ports along an outer surface of the transfer module, which open to a central chamber within the transfer module. The transfer module is designed to move laterally within the cartridge housing. The lateral movement of the transfer module aligns at least a portion of the plurality of first ports with at least a portion of the plurality of second ports.

Description

[0001] This application is a divisional application of the patent application with the title "Test cartridge with integrated transport module", international filing date 15 March 2013, international application number PCT / EP2013 / 055432, national application number 201380024805.3. TECHNICAL FIELD

[0002] Embodiments of the present application relate to the technical field of clinical diagnostic tools. BACKGROUND

[0003] In view of the complexity of the automation of molecular detection and immuno techniques, there is a lack of a product that provides performance sufficient to enable clinical application to near patient point of care testing facilities (point of care testing). Typical molecular detection involves a number of processes including correct dosing of reagents, sample introduction, cell lysis to extract DNA (deoxyribonucleic acid) or RNA (ribonucleic acid), purification steps and amplification for subsequent detection. Even though there are central laboratory intelligent platforms that automate these processes, for a number of tests that require short turn-around times, central laboratories cannot provide results in the required time frame.

[0004] However, it is difficult to implement a system that provides accurate and reliable results in a clinical setting at a reasonable cost. Given the complex nature of a number of molecular detection techniques, results are prone to error if test parameters are not carefully controlled or if environmental conditions are not ideal. For example, existing instruments for PCR (polymerase chain reaction) techniques face high barriers to entry for clinical diagnostic applications due to background from extraneous DNA. In the case of specific pathogen testing, previous reactions performed in pipettes, test tubes or general laboratory equipment are a major source of contamination. In addition, the use of molecular techniques to detect microbial pathogens can produce false negatives. False negatives can result from, for example: improper handling of reagents that inhibit polymerase chain reaction (PCR) such as hemoglobin, urine or saliva; inefficient release of DNA from cells; or inefficient extraction and purification of DNA or RNA.

[0005] The fact that molecular techniques have outstanding levels of sensitivity at concentrations lower than those of the previously referenced methods makes it difficult to draw clinically relevant conclusions while avoiding false positive results that call for errors. In order to minimize this problem, especially for the detection of pathogenic microorganisms, the test must have quantification capacity. Therefore, there is an increasing need to implement multiplexed assays and test arrays to incorporate enough data to draw confident conclusions. As an example, one of the main limitations of existing PCR-based tests is the inability to perform amplification of different target genes simultaneously. Although techniques such as microarrays provide very high multiplexing capacity, the main limitation of these techniques is the low speed of obtaining results, which generally has no positive impact on patient management. SUMMARY

[0006] Clinical diagnostic platforms can integrate multiple analytical test processes to reduce errors, reduce costs, and shorten test times.

[0007] In one embodiment, a system includes a cartridge housing and a hollow transfer module. The cartridge housing further includes at least one sample inlet, a plurality of storage chambers, a plurality of reaction chambers, and a fluidic network. The fluidic network is designed to connect the at least one sample inlet, a portion of the plurality of storage chambers, and a portion of the plurality of reaction chambers to a plurality of first ports located on an interior surface of the cartridge housing. The hollow transfer module includes a plurality of second ports along an exterior surface of the transfer module that open to a central chamber within the transfer module. The transfer module is designed to move laterally within the cartridge housing. Lateral movement of the transfer module aligns at least a portion of the plurality of first ports with at least a portion of the plurality of second ports.

[0008] In one embodiment, the transfer module includes an inner housing that encloses the central chamber and a sheath formed around the inner housing. The sheath includes a patterned ridge along an exterior surface of the sheath. The patterned ridge is designed to form a plurality of valve regions along the exterior surface of the sheath when the transfer module is seated within an enclosing member that is in contact with the patterned ridge. The sheath further includes a plurality of ports that extend through the sheath and the inner housing into the central chamber. The plurality of ports are located within one or more of the plurality of valve regions formed by the patterned ridge. One of the plurality of valve regions having a corresponding port that extends into the central chamber is designed to be pressurized independently of the other valve regions of the plurality of valve regions such that pressurization results in fluid flow into or out of the central chamber via one or more of the plurality of ports.

[0009] An exemplary method is described. The method includes laterally translating a transfer module to align a first port of a transfer module having a central chamber with a port of a first chamber. The method also includes drawing a sample from the first chamber into the central chamber using a first pressure differential. Once the sample is in the central chamber, the method further includes laterally translating the transfer module to align a second port of the transfer module with a port of a second chamber, and drawing the sample from the central chamber into the second chamber using a second pressure differential.

[0010] Another exemplary method is described. The method includes laterally translating a transfer module within a housing to align a structure on the outer surface of the transfer module with a first port associated with a first chamber and a second port associated with a second chamber. The method further includes drawing a sample from the first chamber into the second chamber via structures aligned at the first and second ports. The method continues to draw a sample from the second chamber into a third chamber located within the transfer module via a port penetrating the wall of the transfer module. Attached Figure Description

[0011] The accompanying drawings, which are incorporated herein by reference and form part of this specification, illustrate embodiments of the invention and, together with the description, serve to explain the principles of the invention and enable those skilled in the art to make and use the invention.

[0012] Figure 1 An illustration of a test box system according to an embodiment is shown;

[0013] Figures 2A-2D Various views of the test box system according to an embodiment are shown;

[0014] Figures 3A-3D Various views of the inner housing of the transmission module according to an embodiment are shown;

[0015] Figures 4A-4C Three views of the transmission module sheath according to an embodiment are shown;

[0016] Figure 5A and Figure 5B An illustration of a test box system according to an embodiment is shown;

[0017] Figure 6A and Figure 6B Various views of the test box system according to an embodiment are shown;

[0018] Figures 7A-7F Various views of the transmission module according to an embodiment are shown;

[0019] Figure 8A and Figure 8B A swab within a test kit system according to some embodiments is shown;

[0020] Figure 9 is a simplified diagram illustrating a method implemented by a test cartridge system according to an embodiment;

[0021] Figure 10 is a simplified diagram illustrating a method implemented by a test cartridge system according to an embodiment.

[0022] Embodiments of the present application will be described with reference to the accompanying drawings. DETAILED DESCRIPTION

[0023] While specific configurations and arrangements are discussed, it should be understood that this is done for illustrative purposes only. Persons skilled in the relevant art will recognize that other configurations and arrangements can be employed without departing from the spirit and scope of the description. It will be apparent to those skilled in the relevant art that the application can also be employed in a variety of other applications.

[0024] It should be noted that "one embodiment," "an embodiment," "certain embodiments," certain implementations" or the like means that a particular feature, structure, or characteristic described in connection with the embodiment can be included in at least one implementation of the application. The appearances of the phrase in various places in the specification are not necessarily all referring to the same embodiment, nor are the various embodiments necessarily mutually exclusive, as can be employed in various implementations of the application. Moreover, when a particular feature, structure, or characteristic is described in connection with an embodiment, it is submitted that it is within the purview of persons skilled in the relevant art to effect such feature, structure, or characteristic in connection with other embodiments whether or not explicitly described or claimed.

[0025] Embodiments described herein relate to a test cartridge system for implementing a variety of molecular, immunoassay, or biochemical tests. In embodiments, the test cartridge integrates all of the components necessary to implement such tests into a portable package. The test cartridge can be configured to be analyzed by an external measurement system that provides data about the reactions taking place in the test cartridge.

[0026] In one example, a single test cartridge can be used to implement multiplexed immunoassays with a given sample. The test cartridge contains all of the necessary buffers, reagents, and labels held in sealed chambers that are integrated with the cartridge to implement the immunoassays.

[0027] In another example, a single test cartridge can be used to implement PCR. DNA and / or RNA can be purified from the remaining sample (lysate) via a membrane contained in the test cartridge. The sample can be drained through the membrane, while a separately stored elution solution can remove the DNA and / or RNA and carry it into another chamber to begin the temperature cycling process.

[0028] Any of the tests described above requires some form of liquid transfer. In one embodiment, the test chamber includes a movable, hollow transfer module with multiple ports aligned along the sides of the chamber housing. Liquid can be transferred between the chambers of the housing or flow into or out of the hollow transfer module by applying a pressure differential to the system. In one embodiment, an external actuator is used to apply the pressure differential.

[0029] A major limitation of molecular diagnostic instruments is contamination-related issues such as cross-contamination and residual contamination. The embodiments described herein are designed to essentially eliminate sample-induced contamination of the instrument.

[0030] In one embodiment, the test kit provides a self-contained liquid that is sealed during the manufacturing process. The reagent or sample must not come into contact with the environment or any part of the instrument. This feature of the test kit is equally important for a variety of laboratories and hospitals to ensure the safe disposal of the product after use.

[0031] Further details regarding the components of the test box are described herein with reference to the accompanying drawings. It should be understood that the arrangement of each physical component is not intended to be limiting, and those skilled in the art will recognize, based on the description, that any of the components may be rearranged or modified without departing from the scope or spirit of the invention.

[0032] First Test Box Example

[0033] Figure 1 -4 shows multiple views and components of the test box system according to an embodiment. Figure 1 A test cartridge system 100 is shown, which includes a cartridge housing 102 and a delivery module 104. The test cartridge system 100 may also include other components, such as an analyzer module or various active components, such as a pump or a heater.

[0034] The transfer module 104 includes an inner housing 110, a sheath 108, and a cover 106. According to this embodiment, the sheath 108 is designed to fit around the inner housing 110. In one example, the inner housing 110 is made of a rigid material (such as metal or plastic), while the sheath 108 is made of a compliant (flexible) material (such as rubber or soft plastic). In another example, both the sheath 108 and the inner housing 110 are made of a soft compliant material, which may be the same material or different materials. In another embodiment, the sheath 108 and the inner housing 110 may be manufactured via an overfill process. The cover 106 is designed to seal the ends of the transfer module 104 to prevent leakage. Further details regarding the transfer module 104 are described in detail below with reference to Figures 3 and 4.

[0035] The transfer module 104 is designed to be inserted into the cartridge housing 102 via the chamber bay 120. In one embodiment, the transfer module 104 is configured to be connected to an external actuator (not shown). The external actuator can cause the transfer module 104 to move laterally within the cartridge housing 102 so as to align the ports on the transfer module 104 with the ports on the cartridge housing 102. In another embodiment, the transfer module 104 is configured to move within the cartridge housing 102 via user operation of an external slide.

[0036] The cartridge housing 102 includes a variety of fluid channels, chambers, and reservoirs. For example, the cartridge housing 102 can include a plurality of storage chambers 116 that can contain a variety of buffers or other reagents for use during an assay or PCR process. The storage chambers 116 can be pre-filled with a variety of liquids so that the end user does not need to fill the storage chambers 116 before placing the test cartridge system 100 into an analyzer. The cartridge housing 102 can also include one or more processing chambers 124A-C that are connected to fluid channels along the sides of the cartridge housing 102. The processing chambers 124A-C can be used for a variety of processing and / or wash processes. In one example, chamber 124A is a waste chamber, chamber 124B is an elution chamber for a PCR process, and chamber 124C is a swab elution chamber. In embodiments, the cartridge housing 102 includes a gripping structure 117 to enable easy handling of the test cartridge system 100.

[0037] A sample is introduced into the cartridge housing 102 via the sample port 114 according to embodiments. In one example, the sample port 114 is sized to receive the length of a standard medical swab. Thus, a user can place the swab up to the break point or fully into the sample port 114 and then seal the port with the port cover 112. In another example, the sample port 114 receives a solid, semi-solid, or liquid sample. In embodiments, the cartridge housing 102 includes more than one inlet to introduce a sample.

[0038] The cartridge housing 102 can contain one or more structures that can be used to perform a test, such as a filter, gel, membrane, etc. For example, the cartridge housing 102 can include a membrane housed in the cavity 122. In one embodiment, the membrane is associated with a fluid channel along the outside of the cartridge housing 102. In another embodiment, the membrane can be disposed in any of the processing chambers 124A-C.

[0039] The chambers and channels around the cartridge housing 102 can be sealed by using the covers 118, 126, and 128. The covers can be a thin film that is capable of sealing fluids within the cartridge housing 103. In another embodiment, the covers can be plastic sheets or any other sealing means. In examples, one or more of the covers are transparent.

[0040] The integrated test cartridge system 100 allows a user to place a sample, for example, into the sample port 114, and then place the test cartridge system 100 into an analyzer. In embodiments, all of the reaction steps, including, for example, resuspension lysis, purification, mixing, heating, binding, labeling, and / or detection, can be carried out in the test cartridge system 100 via interaction with the analyzer without requiring end-user intervention. Additionally, from the time all of the liquids are kept sealed in the test cartridge system 100 until after the test is complete, the test cartridge system 100 can be removed from the analyzer and safely disposed of without contaminating the analyzer.

[0041] Figures 2A-2D Multiple views of the cartridge housing 102 are shown, according to embodiments. The description of each view depicts features that can be provided on the cartridge housing 102, but should not be limiting of the placement or dimensional characteristics of the features.

[0042] Figure 2A An example of a side view of the cartridge housing 102 is provided. As such, the view shows multiple chambers, a fluidic network, and a series of ports connecting the multiple chambers, extending into the cartridge housing 102. Each of these groups will be described in more detail herein.

[0043] The multiple processing chambers can include a waste chamber 218, an elution chamber 220, and a swab elution chamber 206. Other types of chambers can also be included, as can be envisioned by those of skill in the relevant art in view of the description. Also, the purpose of each chamber can be different from the names specified herein.

[0044] A plurality of reaction chambers 216 are also shown. Such chambers can have a similar shape to a centrifuge tube, for example. In one embodiment, liquid can be aspirated into the reaction chambers 216 for mixing with reagents that have been pre-loaded into each reaction chamber. For example, each reaction chamber can be loaded with a different DNA probe or real-time PCR master mix, and liquid can be aspirated into each reaction chamber to create a different mixture in each chamber. The reagents can be freeze-dried prior to loading into the reaction chambers 216 or after being loaded into the reaction chambers 216. In another embodiment, the reaction chambers 216 are also used for sample detection. Thus, in one embodiment, the reaction chambers 216 can also be considered detection chambers. Detection can be implemented using an external light source and light detector coupled to an analyzer in which the test cartridge system 100 is placed. Thus, any wall or cover of the reaction chambers 216 can be transparent to allow optical detection. In one example, the light detector measures the absorbance of light through the liquid in the reaction chamber at one or more wavelengths. In another example, the light detector measures a fluorescent signal generated by a fluorescent component in the reaction chamber. In an embodiment, the fluorescent measurement is made from below the reaction chamber 216. The reaction chambers 216 can be adapted for other detection means, such as electrochemical, electromechanical, surface plasmon resonance, etc.

[0045] According to embodiments, a set of smaller channel amplification features 214 are viewed from upstream of the reaction chambers 216. The channel amplification features 214 can act as liquid sensing areas. As such, the channel amplification features 214 can be used in conjunction with an external optical probe to determine whether liquid is present in the channel amplification features 214. Such a determination can be used to activate other functions of the test cartridge system 100. In another embodiment, the channel amplification features 214 can include integrated sensors, such as patterned resistive sensors, to indicate the presence of fluid or flow.

[0046] A plurality of fluidic channels are connected to each chamber or other element within the cartridge housing 102. Each channel is also designed to end in a port that will interface with a port or valve region on the transport module 104. In an embodiment, the cartridge housing 102 includes two rows of primary ports, such as a row of liquid ports 210 and a row of venting / aspiration ports 212. The liquid ports 210 allow fluid to flow into the cartridge housing 102 Figure 2AAny one of the chambers shown or the flow through filter 222. The liquid ports 210 can be either as inlets for drawing liquid from the cartridge housing 102 into the transport module 104 or as outlets for discharging liquid from the transport module into the fluid network of the cartridge housing 102. The vent / suction ports 212 can be used to open a particular fluid pathway to atmosphere, enabling liquid to be drawn into its corresponding chamber. For example, a vacuum pressure can be applied to the leftmost port in the row of vent / suction ports 212, which can allow liquid to enter the waste chamber 218 via the left second port in the row of liquid ports 210. In another example, a vacuum pressure applied from the left second port in the row of vent / suction ports 212 draws liquid from the left third port into the elution chamber 220. In another embodiment, the vent / suction ports 212 can be open to atmosphere.

[0047] Other processing ports 204 can be found to lead to another section of the cartridge housing 102. The processing ports 204 can enter or pass through an inner processing chamber. For example, the inner processing chamber can be a bead beater chamber for lysing any cells in a sample. In another example, a sample containing solid, semi-solid, or liquid material can be placed directly into the inner processing chamber via a second sample inlet. The inner processing chamber homogenizes the material or lysates the cells, and the resulting liquid sample can be drawn from the inner processing chamber to the transport module 104 via an inner port (not shown) of the inner processing chamber.

[0048] The ports can be small holes that extend through the thickness of the cartridge housing 102. In an embodiment, each of the liquid ports 210 is designed to align with another port on the transport module 104, which can move laterally between the various liquid ports 210. In an embodiment, each of the vent / suction ports 212 is designed to align with a region around the transport module 104 that allows or causes the port to be in communication with atmosphere or pressurized. Each port can include a hydrophobic material or can have a particular geometry to prevent leakage through the port in the absence of any applied pressure.

[0049] As shown, the filter 222 can be incorporated within the fluid network. As such, liquid can pass through the filter 222 due to a pressure differential. The filter 222 can include, for example, a silicate matrix for capturing nucleic acid sequences. In another example, the filter 222 can be a membrane for extracting plasma from a whole blood sample. Other filter types are also contemplated, such as a reverse osmosis filter. In another example, the filter 222 can include appropriate materials for an analytical column, for example, to implement a protein purification method.

[0050] Figure 2BAnother example embodiment of a cartridge housing 102 is shown. This embodiment includes many of the same features as the example cartridge housing shown in Figure 2A including the waste chamber 218, the elution chamber 220, and the swab elution chamber 206. However, the fluidic network connected to the liquid port 210 now includes a reaction chamber 224, a chamber 225, and a plurality of detection chambers 226a-e. In one example, a single fluidic path connects each of the reaction chamber 224, the chamber 225, and the detection chambers 226a-e together. A series of channel amplification features 214 are also shown, and serve the same purpose as the channel amplification features in the above-described embodiment in Figure 2A The arrangement of chambers described in this embodiment can be used for immunoassay or other types of binding affinity detection methods.

[0051] The reaction chamber 224 can contain reagents that mix with the sample before being passed to the detection chambers 226a-e. The reagents can be first freeze-dried or freeze-dried reagents can be placed into the reaction chamber 224 and rehydrated upon contact with the liquid sample. The chamber 225 can contain a new set of freeze-dried reagents and can be used during a PCR process to further amplify nucleic acid sequences. In another example, the chamber 225 can contain other reagents to mix with the sample. Alternatively, the chamber 225 can contain a filter or capture probe to separate specific compounds from the sample before passing it to the detection chambers 226a-e.

[0052] Similar to the reaction chamber 216 described above in Figure 2A The detection chambers 226a-e are configured to allow optical interrogation, similar to the reaction chamber 216 described above in

[0053] According to embodiments, Figure 2C A top view of the cartridge housing 102 is shown. A plurality of storage chambers 230A-E are observed and are similar to the storage chambers 116 previously described in Figure 1 According to embodiments, a sample entry window 232 is also disposed at the top of the cartridge housing 102. The sample entry window 232 can be used to place samples into the inner processing chamber. For example, solid samples can be homogenized before testing can begin. These solid samples can be placed into the sample entry window 232 and directly into the inner processing chamber.

[0054] According to an embodiment, the inlets 228 are arranged such that each port is located in a unique storage chamber. At an appropriate time during the testing procedure, the solution stored in each storage chamber 230A-E can be drawn down through the corresponding inlet into the transport module 104. Thus, the transport module 104 also has another port located at the top of the transport module 104 that can be aligned with each of the inlets 228. In an example, the lateral movement of the transport module 104 changes the port in the inlets 228 that is aligned with the top opening of the transport module 104. In another example, the inlets 228 can directly access the fluidic network within the cartridge housing 102 prior to reaching the transport module 104.

[0055] At least one of the storage chambers 230A-E can be configured to receive a sample that has been placed into the cartridge housing 102 via the sample port 114. For example, the storage chamber 230B can be sized to receive a sample cotton swab. In another example, the storage chamber 230B contains a solution to suspend the sample after it has been introduced.

[0056] Figure 2D A view of another side of the cartridge housing 102 (opposite the side shown in Figure 2A In addition, according to an embodiment, the cartridge housing 102 includes a pressurization port 236 and a vent port 234. The pressurization port 236 can be connected to an external pressure source, such as a vacuum pump, a syringe pump, a pressure pump, or the like. In one example, the external pressure source is integrated with an analyzer in which the cartridge housing system 100 is placed. The differential pressure applied to the system via the pressurization port 236 can be used to move liquids through various regions within the cartridge housing 102 and the transport module 104. According to an embodiment, the vent port 234 can be configured to open to the atmosphere. As such, the vent / suction port 212 can access a region around the transport module 104 that is also coupled to the vent port 234. In another example, a pressurization source is connected to the pressurization port 236 to push liquid through the vent / suction port 212. Any number of ports can be included to pressurize various regions within and around the cartridge housing 102 and the transport module 104.

[0057] In one embodiment, the cartridge housing 102 provides a structure configured to center the test cartridge system 100 within an automated analyzer. For example, a plurality of apertures 235a-b can be provided on the cartridge housing 102 to interconnect with corresponding pins on the analyzer to facilitate centering the test cartridge system 100 relative to the external. An oval protrusion can also be used to center the test cartridge system 100 in the center of an automated analyzer. According to an embodiment, the cartridge housing 102 can be configured to be placed in a test cartridge system 100 that is placed in an automated analyzer. Figure 2DThe light access region 240 is disposed below the reaction chambers 216. The light access region 240 is configured to be substantially transparent to all wavelengths used during the light detection process. In one example, each individual reaction chamber has its own light access region. In another example, a single light access region spans multiple reaction chambers 216.

[0058] One or more thin films can be placed over the series of reaction chambers 216. The thin films can be thin enough to still provide a sufficient seal while also allowing for easier heating and / or cooling of the contents within the reaction chambers 216 via an external source. For example, the thin films can be in contact with a surface that is thermally controlled by any one or a combination of a thermoelectric device, a resistive heater, and forced air.

[0059] Figure 3A -D shows a plurality of views around and inside the inner housing 110 of the transport module 104 according to an embodiment. Figure 3A A perspective view of the inner housing 110 according to an embodiment is shown. The inner housing 110 is formed from a box 302, which can be a rigid material. For example, the box 302 can be a hard plastic or a metal material. In another example, the box 302 can be a flexible plastic material.

[0060] The inner housing 110 includes one or more ports that extend through the thickness of the box 302. The ports can include a primary inlet 306 and a transport pressure port 308. In an embodiment, the primary inlet 306 is aligned with the inlet 228 of the cartridge housing 102. In another embodiment, the transport pressure port 308 is aligned with the pressure port 230 of the cartridge housing 102. Figure 2C Each of the inlets 228 is shown aligned.

[0061] In an embodiment, the rails 304 are used to hold the valve sleeve 108 in place around the inner housing 110. The valve sleeve 108 will be described separately in Figure 4A The valve sleeve 108 is described separately in -C. The box 302 can also include a coupling region 310 to connect the transport module 104 to an actuator. The actuator can be mechanized and exert a force on the transport module 104 to cause movement. In another embodiment, the coupling region 310 can be connected to a structure in any manner that allows a user to exert a force to the interface and as a result cause movement of the transport module 104.

[0062] Figure 3B A side view of the inner housing 110 is shown. The view shown is the side facing away from the Figure 3A the side of the inner housing 110. Similar rails 304 are shown on this side of the inner housing 110. In another embodiment, the inner housing 110 includes only a single rail structure. A primary outlet 312 is also shown. In an embodiment, the primary outlet 312 is aligned with the outlet 226 of the cartridge housing 102 as shown in Figure 2AEach of the liquid ports 210 is shown aligned. It should be appreciated that the inner housing 110 can include any number of ports around the surface of the tank 302, and the view shown is not meant to be limiting as to the manner and number of ports.

[0063] Figure 3C A cross-sectional view of the interior of the inner housing 110 is shown. The tank 302 encloses a transfer chamber 316. Also included is a chamber cover 318 to seal fluids or any other sample type within the transfer chamber 316.

[0064] The primary outlet 312 is shown at or near the lowermost portion of the transfer chamber 316. This placement scheme allows for sufficient draining of the transfer chamber 316 through the primary outlet 312. To further facilitate full drainage, in accordance with an embodiment, the interior walls of the transfer chamber 316 are sloped downward. In one example, one or more walls of the transfer chamber 316 are sloped. In one example, a wedge 320 is disposed within the transfer chamber 316 to provide a sloped surface.

[0065] In an embodiment, the transfer chamber 316 contains a stirring element 324. For example, the stirring element 324 can be a magnetic stir bar. The stirring element 324 can be used to effectively mix the contents of the transfer chamber 316. In one example, the stirring element 324 is excited via an external magnetic field. In an embodiment, the cartridge housing 102 includes one or more magnets disposed along the path of motion of the transfer module 104. The magnets are disposed to induce a magnetic force on the stirring element 324, causing it to move within the transfer chamber 316. In another example, the stirring element 324 is physically connected to an actuator configured to move the stirring element 324.

[0066] Figure 3D A perspective view of the lid 106 is shown, in accordance with an embodiment. The lid 106 can include two chamber covers 3118 and a wedge 320 connected to the chamber cover 318. Integrating the wedge 320 with the chamber cover 318 allows for further simplification of the manufacturing process.

[0067] Returning to Figure 3AThe plurality of ports disposed about the inner housing 110 can be used to transfer liquid between the various chambers of the cartridge housing 102 and the transfer module 316. In an example process, the transfer module 104 is moved laterally so that the primary inlet 306 is aligned with one of the plurality of inlets 228 of the cartridge housing 102. Once aligned, a vacuum pressure can be applied via the transfer pressure port 308 that draws liquid from a storage chamber of the cartridge housing 102 into the transfer chamber 316 of the transfer module 104. Further lateral movement of the transfer module 104 causes the primary inlet 306 to align with a different one of the plurality of inlets 228 of the cartridge housing 102. A second applied vacuum pressure draws liquid from another storage chamber of the cartridge housing 102 into the transfer chamber 316. The two liquids within the transfer chamber 316 can be further mixed as desired with the agitation element 324. A third lateral movement of the transfer module 104 causes the primary outlet 312 to align with one of the liquid ports 210 of the cartridge housing 102. A positive pressure applied at the transfer pressure port 308 expels liquid from the transfer chamber 316 through the primary outlet 312 and into the fluid network of the cartridge housing 102 via the aligned liquid outlet. It should be appreciated that more liquid drawing and expelling procedures can be implemented and it should be appreciated that liquid can also be drawn into the transfer chamber 316 via the primary outlet 312.

[0068] To control the flow of fluid along the special fluid channels and to control pressurization of the area outside the transfer module 104, a valve system is implemented about the inner housing 110. Figure 4A -C shows a plurality of views of the valve sleeve 108 disposed about the inner housing 110.

[0069] Figure 4A A perspective view of the valve sleeve 108 according to an embodiment is shown. The valve sleeve 108 includes a compliant sleeve 402 that fits about the inner housing 110. The compliant sleeve 402 can be a flexible material such as rubber. In an embodiment, the outer surface of the compliant sleeve 402 includes ports that extend through the thickness of the compliant sleeve 402 and align with ports on the inner housing 110. For example, a first port 410 can align with the primary outlet 312 while a second port 412 can align with the primary inlet 306.

[0070] According to embodiments, the outer surface of the compliant sleeve 402 can also include various patterned ridges and shaped features. For example, annular ridges 404 along the sides of the valve sleeve 108 can align with each of the vent / suction ports 212. Other annular structures 414 can be found along the top of the valve sleeve 108. The solid annular structures 414 can be flush with each of the plurality of inlets 228 in order to prevent inadvertent pressurization of each port. The solid annular structures 414 are preferred for long-term liquids stored in the storage chambers 230a-e. Hollow annular features provide the benefit of reducing friction as the transfer module 104 moves within the cartridge housing 102.

[0071] Other patterned ridges can also be provided. For example, scalloped ridges 406 can extend along the length of the valve sleeve 108 in order to seal any of the plurality of liquid ports 210 that are not aligned with the first port 410. In another example, straight ridges 408 ensure that uniform pressure is applied to the inner surface of the cartridge housing 102.

[0072] The pattern of ridges is designed to press against the inner wall of the cartridge housing 102. This creates a plurality of regions around the outer surface of the transfer module 104 that are sealed from one another. Thus, an applied pressure differential in one region will not affect the pressure in another region. This example design can be more clearly seen in Figure 4B

[0073] Figure 4B A cross-section of the transfer module 104 within the transfer chamber 102 is shown according to embodiments. The inner housing 102 and the valve sleeve 108 of the transfer module 104 are shown, as well as protrusions 416 that protrude from the valve sleeve 108. The protrusions 416 can be similar to the previously described ridges and annular features. According to embodiments, the protrusions 416 press against the inner wall of the cartridge housing 102 in order to create a plurality of valve regions, such as regions 418A-C. For example, region 418B is separated from regions 418A and 418C by the protrusions 416, and as such, can be pressurized independently of regions 418A and 418C. Figure 4A

[0074] In one example, the regions 418 are associated with pressurization ports 236( Figure 2D ) on the sides of the cartridge housing 102. An applied pressure differential via the pressurization ports 236( Figure 2D ) will also pressurize region 418B, while not pressurizing the surrounding regions that are separated by the protrusions 416.

[0075] ​​The cross-sectional view also shows how the first port 410 of the transfer module 104 is aligned with one of the liquid ports 210 of the cartridge housing 102. The protrusion 416 can enclose the port 410 in order to prevent fluid leakage or unintentionally pressurizing the port area.

[0076] Figure 4C A side view of the valve sleeve 108 is shown according to an embodiment. The side view shown is the side facing away from the side of the cartridge housing 102. Figure 4A According to an embodiment, the valve sleeve 108 also includes a pressure port 420 that can be aligned with the transfer pressure port 308 of the inner housing 110. The pressure port 420 is disposed in a pressurized area 424 defined by various ridges, such as straight ridges 428 and serpentine ridges 422. The pattern and / or shape of the ridges is not limited to those shown. According to an embodiment, another area 426 exists on the other side of the serpentine ridges 422. The area 426 can be similar to the area 424 with reference to the cartridge housing 102. Figure 4B The area 426 is considered with reference to the cartridge housing 102. Figure 4C The area 426 is considered with reference to the cartridge housing 102.

[0077] According to an embodiment, the pressurized area 424 is associated with a port of the cartridge housing 102. For example, the pressurized port 236 can be located within the pressurized area 424 when the transfer module 104 is located within the cartridge housing 102. In one example, the pressurized port is located below the middle horizontal portion of the serpentine ridges 422. According to an embodiment, the pressurized area 424 remains associated with the pressurized port 236 as the transfer module 104 translates within the cartridge housing 102. In another example, the translation of the transfer module 104 due to the serpentine shape associated with the serpentine ridges 422 can cause the vent port 234 within the pressurized area 424 and the pressurized port 236 within the area 426 to be in line. The pressure differential applied via the aligned ports within the pressurized area 424 will also apply the same pressure differential in the transfer chamber 316 via the pressure port 420. In another example, the translation of the transfer module 104 causes the pressurized port 236 to align with various areas around the outer side surface of the valve sleeve 108.

[0078] According to an embodiment, the area 426 is also associated with a port of the cartridge housing 102. For example, the vent port 234 can be located within the area 426, such as directly above the middle horizontal portion of the serpentine ridges 422. In this example, the area 426 is open to atmospheric pressure. Alternatively, the pressurized port 236 can be located within the area 426, for example, between the bends of the serpentine ridges 422. A vacuum pressure can be applied at the pressurized port 236 that similarly pressurizes the area 426.

[0079] According to an embodiment, the area 426 can fold over to the other side of the valve sleeve 108 Figure 4AThe region around the annular ridge 404 and the region of the annular structure 414 can thus be considered to be the same region as the region 426. In the exemplary embodiment, the annular ridge 404 covers all but one of the vent / suction ports 212 as the transport module 104 moves between the discontinuities in the stepped portion of the cartridge housing 102, according to the embodiment. The one vent / suction port not covered by the annular ridge 404 will then be subjected to atmospheric pressure or a differential pressure that has been applied to the region 426.

[0080] Second test cartridge embodiment

[0081] Figs. 5-8 show various views and components of a test cartridge system according to another embodiment. Figures 5A-5B An exploded view of a test cartridge system 500 is shown that includes a cartridge housing 502 and a transport module 504. The transport module 504 functions substantially the same as the transport module 104 of the first test cartridge embodiment within the system. According to the embodiment, the transport modules 504, 104 both move laterally within the system so as to line up the ports on the exterior of the transport module with the ports on the sides of the housing 502, 102. Also, the transport module 504 has a similar configuration as the transport module 104, in that the inner housing 510 is surrounded by a sheath 508 and has an inner chamber covered by a cover 506. Reference is made to the description of the transport module 104 for further details. Figure 7A -D Additional details of the transport module 504 are described below.

[0082] According to some embodiments, the housing 502 includes many of the same features as the housing 102. For example, the housing 502 includes multiple processing chambers 524a-b, a chamber bay 520 for receiving the transport module 504, and a sample port 514 with a port cover 512. In one example, the chamber 524a is a waste chamber and the chamber 524b is a swab receiving chamber. According to one embodiment, the sample port 514 opens into the chamber 524b, which can be sized to receive the length of a medical swab. According to embodiments, the housing 502 also includes multiple covers 518, 526, 527, and 528 for sealing various chambers and passageways around the housing 502. In one example, each of the covers 526 and 518 are made of substantially the same material as the housing 502. In embodiments, any of the covers 526, 528, and 518 are substantially transparent. The cover 527 can be a material with a high thermal conductivity, such as aluminum foil, to allow for more efficient transfer of heat to the sample within the housing 502. An opening 513 can be formed in the cover 526 so that heat can be more efficiently transferred from the cover 527 to the inner processing chamber of the housing 502 via the opening 513. The inner processing chamber can also have its own access port with a cover 532. In embodiments, the housing 502 includes a top opening 522 for receiving various types of filters to be placed into the housing 502. In one example, solid phase extraction materials such as membranes or silica beads can be placed into the chambers of the housing 502 via the top opening 522. According to some embodiments, multiple openings can be found in the covers 526 and 527. The openings of the cover 526 can be flush with the multiple small chambers of the housing 502 to, for example, allow for more generous space for providing desiccant to be placed into the small chambers. In another example, the openings of the cover 527 can be positioned so that light has access to the sensing region of the passageway of the housing 502.

[0083] According to embodiments, the housing 502 also includes an opening 515 that opens into an inner processing chamber. Any type of sample, such as a solid, semi-solid, or liquid sample, can be placed into the inner processing chamber via the opening 515. The opening 515 can be covered by a cover 532 to prevent any leakage of the sample placed into the inner processing chamber. The inner processing chamber can be, for example, a ball mill chamber for lysing cells or homogenizing the sample. The housing 502 can be sized to accommodate ball mill modules of different sizes. In embodiments, the ball mill module within the housing 502 accepts a liquid volume in the range of 10 milliliters to 5000 milliliters. In another embodiment, the ball mill module accepts a volume between 100 milliliters and 1000 milliliters.

[0084] Figure 6A and Figure 6B A side view of the housing 502 according to some embodiments is shown in more detail.Figure 6A A variety of storage chambers on the side of the housing 502 are shown. According to embodiments, the housing 502 includes seven storage containers 630a-g. Other numbers of storage containers are also possible. It should also be understood that the shapes and sizes of the variety of storage containers 630-g shown are not intended to be limiting and can vary to include virtually any shape and size. Each of the variety of storage containers 630a-g can include two openings into the container. A first opening can be coupled to a fluid channel to transfer fluid into or out of the container, while a second opening can allow the container to communicate with atmospheric pressure. The ability to vent the container can allow for more efficient emptying of the container when fluid is being drawn from it. Also, if air can escape from the vent, air will not be trapped within the container as fluid is moved into it.

[0085] Two chambers, a first buffer chamber 642 and a second buffer chamber 643 are also shown. According to embodiments, each buffer chamber can be used to assist in preventing liquid from leaving the fluid infrastructure of the test cartridge system. For example, the first buffer chamber 642 can be designed to hold any "spilled" liquid that inadvertently runs down the channels used to vent the system. The venting channels can also include a liquid sensing area. If liquid passes the liquid sensing area, a sensor can be designed to cut off any external force causing fluid flow in order to stop the liquid before it can escape from the vent. Similarly, the second buffer chamber 643 can be designed to hold any "spilled" liquid that runs down from the tubing used to apply pressure to the system. In some embodiments, the external pressure is a vacuum pressure used to draw liquid through the variety of channels and chambers of the test cartridge system 500. The pressure channels can also include a liquid sensing area with an associated sensor designed to work in a similar manner to the previously described sensor in the venting channels. Additionally, according to some embodiments, each port associated with the first buffer chamber 642 and the second buffer chamber 643 can include a filter 641a and 641b. The filters 641a and 641b can be aerosol filters to prevent contamination of the rest of the system when using the ports to vent and / or pressurize the system.

[0086] In embodiments, the housing 502 includes clamping points 635a and 635b to support the housing 502 in a larger analyzer system. The test cartridge can be placed into an analyzer that includes components to heat and / or cool the system, optionally measure certain chambers, provide a vacuum or pump source, and actuate movement of the transport module 504. The housing 502 of the test cartridge system 500 can be held in place within the analyzer via the clamping points 635a and 635b so that the housing 502 does not move while the various operations of the analyzer are being performed.

[0087] A waste channel 641 can also be included in the housing 502 for directing fluids and any other waste samples into a waste chamber, such as, for example, chamber 524a. The inlet into the waste chamber can be designed to only allow fluid to flow into the chamber and not out of the chamber.

[0088] Figure 6B Another example embodiment of the opposite side of the housing 502 is shown. The example fluidic device is provided with a plurality of ports 610 in a row for fluidic coupling with the ports of the transport module 504. A pressure port 636 and a vent port 634 are also shown. According to an embodiment, the pressure port 636 can be connected to an external pressure source for applying a positive or negative pressure differential throughout the system. The vent port 634 can either be in communication with atmospheric pressure or connected to another pressure source. For example, a positive pressure differential can be applied to one port and a negative pressure differential to the other port to cause the liquid to move more rapidly through the coupled channels of the system.

[0089] The housing 502 also includes a reaction chamber 616, which can be operated in a similar manner as the reaction chamber 216 described above with respect to the test cartridge system 100. Figure 2A The reaction chamber 616 is operated in a similar manner as the reaction chamber 216 described above. In an embodiment, the plurality of channels leading to the reaction chamber 616 includes a premix chamber 631. The premix chamber 631 can include a dry chemical, such as a desiccant or a lysing agent. In another example, the premix chamber 631 includes a dry chemical bead or a biological sample. Such biological or chemical compounds can be stored in the premix chamber 631 for long periods of time prior to use. According to an embodiment, the premix chamber 631 can be sized to specifically match the size of the dry chemical bead, which is typically on the order of a few millimeters in diameter. In one example, the fluid drawn to the reaction chamber 616 mixes with the sample stored in the premix chamber 631. According to an embodiment, the plurality of channels also includes a sensor region 614. The sensor region 614 can be used to determine the presence or absence of liquid and / or the flow of liquid within the corresponding channel. An external optical probe can be used with the sensor region 614 to make the determination. In another example, an integrated sensor, such as a resistive sensor, can indicate the presence or absence of liquid or the flow of liquid. The data output from the sensor region 614 can be used by the control system to activate various functions of the test cartridge system 500 or to control the flow of liquid within the corresponding channel having the sensor region 614.

[0090] Also shown are a plurality of frits 633 located on the sides of the housing 502. Each frit 633 can comprise a plurality of materials designed to filter or capture a plurality of particle sizes. In one example, the frits 633 are plastic materials having thin mesh with optional pore sizes that can range from 0.1 microns to 500 microns. In one embodiment, the frits 633 have a pore size of approximately 20 microns.

[0091] According to embodiments, in Figure 6B The lower portion of the cartridge housing 502, the light access region 640 is disposed below the reaction chamber 616. The light access region 640 is designed to be substantially transparent to all wavelengths used during the light detection process. In one example, each individual reaction chamber has its own light access region. In another example, a single light access region spans a plurality of reaction chambers 616. In one example, the light detector measures the absorbance of light by the liquid within the reaction chamber 616 at one or more wavelengths. In another example, the light detector measures the fluorescent signal generated by a fluorescent compound within the reaction chamber 616. The fluorescent measurement can be taken from below the reaction chamber 616 or from the side of the reaction chamber 616. The reaction chamber 216 can be adapted for other detection means, e.g., electrochemical, electromechanical, surface plasmon resonance, etc.

[0092] Figures 7A-7F A plurality of views in and around the transfer module 504 according to some embodiments are provided. A plurality of the general features of the transfer module 504 are substantially similar to those of the transfer chamber 104 of the first test cartridge embodiment. For example, both transfer modules comprise a compliant material wrapped over a harder inner housing and have ports on the outside that open into a central chamber. However, the arrangement and design of the specific features on the transfer module 504 recognize other considerations as discussed with respect to Figures 7A-7F As provided herein.

[0093] According to some embodiments, in Figure 7A and 7BTwo isometric views are shown from different sides of the transfer module 504. The transfer module 504 includes a sheath 508 that surrounds an inner housing 510. The transfer module 504 also includes two ports 712a and 712b. In embodiments, each of the ports 712a and 712b are disposed on a lower portion of the transfer module 504. In one example, the ports 712a and 712b are substantially opposite each other. The transfer module 504 can also include a third port 706 along a top portion of the transfer module 504. In embodiments, the ports 712a, 712b, and 706 open into a central chamber inside the transfer module 504. Any of the ports 712a, 712b, and 706 can be used to couple to the various ports of the housing 502 for fluid transfer. In another example, any of the ports 712a, 712b, and 706 can be coupled to a pressurized source for applying a pressure differential to a fluid within the test cartridge system 500. In one embodiment, the ports 712a and 712b are used only for fluid transfer, while the port 706 is used to pressurize or depressurize the central chamber of the transfer module 504.

[0094] According to embodiments, the transfer module 504 also includes various patterned ridges and shaped features. Similar to the patterned structure of the sheath 108 on the transfer module 104, the patterned regions on the transfer module 504 can align with the various ports of the housing 503 and define various pressurized regions or valves around the transfer module 504. For example, the annular structure 704 can be flush with a port on the housing 502 to seal the port. According to embodiments, a cluster of annular structures 714 is also provided. Based on the position of the transfer module 504, the cluster of annular structures 714 can be arranged to be flush with various ports of the housing 502. In one embodiment, an annular structure from the cluster of annular structures 714 acts as a fluidic coupling between at least two ports of the housing 502. In an example, fluid can flow from one channel to another by flowing through two ports that are flush with the same annular structure. In this way, fluid can be moved through different channels of the housing 502 without having to pass through the central chamber of the transfer module 504. According to embodiments, fluid can also flow into or out of the central chamber of the transfer module 504 via any of the ports 712a, 712b, and 706.

[0095] The sheath 508 of the transport module 504 can also include various ridges 707 and 709. In an embodiment, the ridges 707 are used to seal various ports 610 of the housing 502, but only one of the ports 610 from the ports 610 is aligned with the port 712a. The ridges 709 can be used to demarcate various regions, such as, for example, regions 711 and 713. In one embodiment, the regions 711 and 713 represent regions that can be pressurized individually. For example, the region 711 can be pressurized via the pressure port 636 as a result of the position of the transport module 504 within the housing 502. Pressurizing the region 711 can correspondingly pressurize and draw fluid into or out of the central chamber of the transport module 504 via the port 706.

[0096] According to an embodiment, a coupling region 702 is also shown on the transport module 504 for coupling the transport module 504 to an actuator. The actuator can be designed to translate the transport module 504 laterally within the housing 502, substantially similar to the first test cartridge embodiment described above.

[0097] Figure 7C A cross-sectional view of the transport module 504 along the length of the transport module 504 is shown according to an embodiment. The transport module 504 includes a central chamber 716. A cover 506 is used to seal the end of the central chamber 716. In one embodiment, the cover 506 is designed to be removable. According to one embodiment, the cover 506 extends into the central chamber 716 so as to provide a sloped surface (surfaces) to facilitate draining any liquid within the central chamber 716. A hole 708 is disposed substantially in the middle of the cover 506 within the central chamber 716 for transporting liquid from / to other regions of the housing 502 to / from the central chamber 716. A transport channel 710 can be such that liquid is directed towards either or both of the ports 712a and 712b.

[0098] Figure 7D A view of the cover 506 including a faceplate 718 and a sloped structure 720 is provided according to an embodiment. The faceplate 718 can be used to seal the end of the central chamber 716, while the sloped structure 720 provides a sloped surface to, for example, facilitate movement of a liquid sample within the central chamber 716 towards either the port 712a or 712b. According to an embodiment, the hole 708 is also shown at the lowermost portion of the sloped structure 720 so as to sufficiently drain all liquid when draining the central chamber 716.

[0099] According to an embodiment, Figure 7EAnother view showing the aperture 708 and the transfer channel 710 is shown from below the cover 506. One example includes a side channel 715 to align the liquid with ports 712a and 712b on the side of the transfer module 504. The channel configuration shown is merely one example for directing fluid into and out of the central chamber 716 and should not be considered limiting.

[0100] According to an embodiment, Figure 7F A cross-sectional view of the transfer module 504 along the width of the transfer module 504 is shown. The sheath 508 is found surrounding the inner housing 510. According to an embodiment, the sheath 508 includes a plurality of protrusions 724. The protrusions 724 can represent a plurality of patterned structures on the sheath 508. In one example, the protrusions 724 press against the inner wall of the housing 502 to create a plurality of zones 722a, 722b, and 722c. Each zone can be pressurized based on the position of the transfer module 504 within the housing 502. According to an embodiment, the ports 712a and 712b are shown aligned with one of the ports 610 of the housing 502 and a port associated with the pressure port 626, respectively. The ports 712a and / or 712b can align with different ports 610 of the housing 502 as the transfer module 504 moves laterally within the housing 502. According to an embodiment, the angled structure 720 and the side channel 715 are shown within the central chamber 716. In an exemplary embodiment, the side channel 715 is connected to each of the ports 712a and 712b in a U-shape.

[0101] According to some embodiments, Figure 8A and Figure 8B A swab is shown inserted into a test cartridge system for analysis. Figure 8A A swab is shown inserted into the chamber 524b of the cartridge housing. The chamber is sealed with the port cover 512. In one example, the swab 802 has a length of approximately 80 mm. It should be understood that the chamber 524b can be sized to receive a swab of any length without departing from the scope or spirit of the present invention.

[0102] Figure 8B Another embodiment is shown in which a longer swab 806 is inserted into the chamber 524b and sealed by an extended cover 804. The extended cover 804 can be used to seal a swab that is longer than the chamber 52b and protrudes from the opening of the chamber. In one example, the longer swab 806 has a length of approximately 100 mm. The longer swab 806 can be bent and / or folded within the chamber 524b.

[0103] Exemplary method of operation

[0104] Exemplary methods for transferring fluid between the various chambers of the two embodiments of the cartridge housing and their corresponding transfer chambers are described below.

[0105] Figure 9 A flowchart of an exemplary method 900 for transferring liquid through the first embodiment of the test cartridge system 100 is shown. It should be understood that the method 900 describes one example sequence of operations that can be implemented with the test cartridge system 100 and should not be considered limiting. Moreover, the method 900 can also be implemented using the second embodiment of the test cartridge system 500.

[0106] At block 902, according to embodiments, the transfer module 104 is moved laterally within the cartridge housing 102 so as to align the inlet of the transfer module 104 with the outlet of the first chamber. The inlet of the transfer module 104 can be, for example, the primary inlet 306. The outlet of the first chamber can be, for example, any one of the inlet 228 row.

[0107] At block 904, according to embodiments, the sample is drawn from the first chamber into the transfer chamber 316 via an applied first pressure differential. In embodiments, the applied pressure differential is applied at the transfer pressure port 308. The applied pressure differential can be a vacuum pressure in order to draw the sample into the transfer chamber 316. The sample can be introduced into the first chamber from a cotton swab or a liquid. The first chamber can be, for example, the inner processing chamber or the processing chamber associated with the sample port 114. Additionally, the sample can be any mixture of liquids, semi-solids, solids, etc.

[0108] At block 906, according to embodiments, the transfer module 104 is moved laterally within the cartridge housing 102 so as to align the outlet of the transfer chamber 316 with the inlet of the second chamber. The outlet of the transfer chamber 316 can be, for example, the primary outlet 312. The inlet of the second chamber can be, for example, any one of the liquid port 210 row. As such, the inlet of the second chamber can lead to any of the chambers of the cartridge housing 102, such as the waste chamber 218, the reaction chamber 216, the swab elution chamber 206, etc.

[0109] At block 908, according to embodiments, the sample is drawn from the transfer chamber 316 into the second chamber via an applied second pressure differential. The second pressure differential can be a positive pressure applied at the transfer pressure port 308. Alternatively, the second pressure differential can be a vacuum pressure applied at the vent / draw port 212 in order to draw the liquid into the chamber associated with the corresponding vent / draw port 212.

[0110] It should be understood that more liquid aspiration procedures can be implemented given the description as would be understood by one of ordinary skill in the relevant art. For example, after module 904, the transfer chamber can have its inlet aligned with a second outlet along the top of the cartridge housing 102 so as to aspirate another liquid stored in another storage chamber. This procedure can be implemented as many times as necessary according to the method required for the particular molecular test.

[0111] In another embodiment, after module 908, other steps can be implemented so as to aspirate the sample back into the transfer chamber and to expel the liquid into a third chamber. For example, the second chamber can be the swab elution chamber 206 and the third chamber can be one of the detection chambers 216. Any number of chambers can aspirate or expel liquid as many times as necessary. Thus, the system allows for an infinite number of liquid transfer patterns among the various chambers.

[0112] Figure 10 A flowchart illustrating an exemplary method 1000 for transferring liquid through the second embodiment of the test cartridge system 500 is shown. It should be understood that the method 1000 describes one example sequence of operations that can be implemented with the test cartridge system 500 and should not be considered limiting.

[0113] According to an embodiment, at module 1002, the transfer module 504 moves laterally within the cartridge housing 502 so as to align structures on the outer surface of the transfer module 504 with a first port associated with a first chamber and a second port associated with a second chamber. The first chamber can be, for example, the input receptacle 622 and the second chamber can be any one of the storage receptacles 630a-g. According to an embodiment, the structures on the outer surface of the transfer module 504 can have a ring shape so as to fit around the first and second ports.

[0114] At module 1004, according to an embodiment, the sample is aspirated from the first chamber to the second chamber via at least the structures on the outer surface of the transfer module 504. In this way, the sample can move between the first and second chambers while at the same time not passing through, for example, the central chamber of the transfer module 504.

[0115] At module 1006, according to an embodiment, the sample is aspirated from the second chamber to a third chamber. The third chamber can be the central chamber 716 of the transfer module 504 and the liquid can enter the central chamber 716 via a port through the wall of the transfer module 504. The port can be, for example, the port 718. Figure 7A and 7BAny one of the fluid ports 706, 712a, or 712b shown herein. The third chamber may include components for mixing or filtering samples. In other embodiments, the transfer module 504 may be laterally movable so that a port of the transfer module 504 is aligned with another port of the housing 502 and the sample in its central chamber is discharged through the aligned port. It should be understood that further liquid aspiration procedures may be implemented in light of the content described herein, as will be understood by those skilled in the art (and other related art forms).

[0116] Example

[0117] Two exemplary methods implemented using the test kit system 100 are now discussed. The first exemplary method relates to real-time PCR detection, while the second exemplary method relates to immunoassay. It should be understood that the steps referenced herein provide feasible examples of using the system and implementing each test.

[0118] PCR method

[0119] An exemplary PCR method uses multiple processing chambers and reaction chambers located around the casing 102. In one example, the PCR method uses... Figure 2A The example of the housing shown is illustrated. It should be understood that alternatives can also be used. Figures 6A-6B The method is implemented using a housing embodiment shown below. In this example, five storage chambers are used, and each storage chamber contains a pre-loaded solution. The storage chambers are labeled as follows.

[0120] R1: Contains Wash-2 buffer

[0121] R2: Contains lysis buffer

[0122] R3: Contains elution buffer

[0123] R4: Contains Wash-3 buffer

[0124] R5: Contains Wash-1 buffer

[0125] The example PCR procedure can be implemented using the process described with reference to the example test kit system 100 above. Similar steps can also be implemented using the various chambers and channels shown on the kit system 500. The sample is introduced into the test kit system 100 via a swab in the swab receiver 114. Alternatively, the sample can be introduced directly into the inner processing chamber via a second inlet for lysis by an integrated ball mill system.

[0126] Once the sample has been introduced into the test cartridge system 100, the entire test cartridge is placed into an analyzer. The analyzer is provided with an actuator for moving the transport module 104, one or more heating elements to perform the PCR reaction, and optical measurement components. The analyzer can also be coupled to the pressure port around the cartridge housing 102 and apply the required pressure differential.

[0127] The transport module 104 is adjusted so that lysis buffer is drawn from R2 into the transport chamber. The transport module 104 is adjusted so that the lysis buffer is moved into the swab elution chamber 206 where the sample from the swab is resuspended in the lysis buffer. The sample then moves with the lysis buffer via the process port 204 to the inner process chamber for lysis of the cells in the sample and release of the DNA and / or RNA. After the lysis procedure, the sample is hereinafter referred to as "lysisate".

[0128] The lysisate is drawn from the inner process chamber back to the transport chamber via the vacuum pressure applied at the transport chamber. The transport module 104 then moves laterally so that its outlet is aligned with the port associated with the waste chamber. However, a filter is arranged upstream of the waste chamber in order to capture DNA sequences. Thus, after applying positive pressure to the transport chamber, the lysisate passes in-line through the filter to the waste chamber. The DNA will be retained in the filter, while most of the unwanted material will pass through the filter to the waste chamber. The filter can for example be a silicate matrix or a plurality of silica beads for capturing nucleic acid sequences.

[0129] The transport module 104 moves to align with R5 and draws wash-1 buffer into the transport chamber. Subsequently, the wash-1 buffer passes through the filter in order to further remove any unwanted material in the filter. The buffer is passed to the waste chamber. A second wash step is then performed with the wash-1 buffer. The transport module 104 aligns with Rl in order to draw in wash-2 buffer and moves again in order to align with the fluid passage containing the filter, wash-2 passes through the filter and is passed to the waste chamber.

[0130] At this stage, it is necessary to clean the transport chamber before it can bring the DNA back to the transport chamber. As such, the transport module 104 aligns with R4 and wash-3 buffer is drawn into the transport passage. The wash buffer can be mixed around the transport chamber. Additionally, the wash-3 buffer can for example be transported to the inner process chamber.

[0131] The transfer module 104 moves laterally to align its top inlet with the outlet of R3. A vacuum pressure is applied to draw the eluent buffer into the transfer chamber. Thereafter, the transfer module 104 moves laterally to align its outlet with the port connected to the eluent chamber 220 on the housing 102. The eluent buffer moves into the eluent chamber 220 via an external positive pressure applied to the transfer chamber or via a vacuum pressure from a vent / suction port connected to the eluent chamber 220.

[0132] The DNA is now ready to be removed from the filter and brought back to the transfer chamber. Using vacuum pressure, the eluent is aspirated from the elution chamber 220 of the housing 102 through the filter back to the transfer chamber, which is aligned with the correct port for receiving the DNA solution. The transfer module 104 then sequentially moves between the ports of the respective reaction chambers via an applied positive pressure, delivering the liquid to each chamber.

[0133] Each reaction chamber contains the reagents required for PCR against DNA. In this example, the reagents are pre-loaded, freeze-dried pellets containing any reagents required for PCR. The reagents are rapidly rehydrated as the DNA solution is brought into each chamber.

[0134] Once the DNA has been transferred to one or more reaction chambers, the analyzer can perform the remaining processing. Specifically, heating and cooling cycles can be performed to activate, denature, anneal, and extend the DNA. Once the cycle is complete, the analyzer's optical measurement system collects data from each reaction chamber to provide test results to the end user.

[0135] Immunoassay

[0136] The exemplary immunoassay uses at least three storage chambers and various processing chambers surrounding the casing 102. In one example, the immunoassay uses... Figure 2B The example shown is a housing. Similar to PCR methods, the storage chamber contains a pre-loaded solution for performing analytical tests. Additionally, specific capture antibodies can be immobilized in the detection chamber 226 to provide binding sites to the antigen of interest. Fluorescently labeled antibodies can also be pre-loaded into the reaction chamber 224 in a lyophilized state. In this example, the storage chamber is labeled as follows:

[0137] R1: Wash-1 buffer

[0138] R2: Buffer

[0139] R3: Wash-2 Buffer

[0140] For clarity, the workflow described herein can be performed for an immunoassay with reference to the exemplary test cartridge system 100. The sample is introduced into the cartridge housing 102 through the inlet of the through-put inner processing chamber. Once introduced, the test cartridge system 100 is placed into an analyzer. The remainder of the method can be implemented by the analyzer system. The transfer module 104 is laterally aligned with the inner processing chamber and draws the sample into the transfer chamber via an applied vacuum pressure.

[0141] Once the sample is inside the transfer chamber, the transfer module 104 is again laterally moved so that its outlet is aligned with the port leading to the elution chamber. The sample from the elution chamber then moves to the transfer chamber by way of the membrane used to obtain plasma from the whole blood. Once the plasma sample, containing the antigen of interest, is returned to the transfer chamber, the transfer module 104 can be aligned with R2 and draw the buffer into the transfer chamber. The buffer mixes with the plasma sample in the transfer chamber.

[0142] Once the mixed plasma sample and buffer, the transfer module 104 is again laterally moved so that its outlet is aligned with the port leading to the reaction chamber 224, which has the lyophilized fluorescently labeled antibodies. The mixture of sample and buffer is used to rehydrate the fluorescently labeled antibodies within the reaction chamber 224. The rehydrated fluorescent antibodies, sample plasma, and buffer combine and mix together. At this stage, if the antibody of interest is present in the mixture, the fluorescently labeled antibodies will bind to the antibody of interest. In embodiments, heating and / or mixing can be implemented to enhance the reaction.

[0143] The formed mixture is transported from the reaction chamber 224 into each of the detection chambers 226. Again, the mixture can be mixed slightly or heated in each detection chamber 226 in order to ensure that the capture antibodies and the antigens within the mixture react with each other.

[0144] Once the mixing is complete, the transfer module 104 is aligned with Rl and draws the wash- 1 buffer into the transfer chamber. The wash- 1 buffer can first be transferred into the reaction chamber and then drawn into each of the detection chambers containing the mixture. The wash- 1 buffer cleans away any unbound material. The wash- 1 buffer continues through the detection chambers and into the waste chamber.

[0145] A second wash step can be implemented. The transfer module 104 is aligned with R3 and draws the wash- 2 buffer into the transfer chamber. The wash- 2 buffer can first be transferred into the reaction chamber and then transferred into each of the detection chambers containing the mixture. The wash- 2 buffer cleans away any unbound material. The wash- 2 buffer continues through the detection chambers and into the waste chamber. At this stage, any bound material to the capture antibodies should be the antigen of interest along with the bound fluorescently labeled antibodies.

[0146] Now the optical measurement system of the analyzer can be used for each detection chamber in order to quantify the amount of antibody based on the received fluorescence signal. The collected data can be annotated again on the standard curve performed previously by the calibrator, for example, to obtain a quantitative result for the end user.

[0147] It should be understood that at the end of each of the methods described above, the entire test cartridge system 100 can be removed from the analyzer and disposed of safely. In another embodiment, one or more of the solutions formed in the detection chambers can be drawn off for use in other analyses. Because the system is a self-contained system, multiple test cartridges can be used with the same analyzer without concern for cross-contamination or build-up between experiments.

[0148] It is to be understood that the detailed description is intended to be illustrative and not restrictive. Numerous other embodiments will be apparent to those skilled in the art in view of the teachings herein. Therefore, the scope of the application is not limited to the embodiments described herein but only by the claims that follow.

[0149] Embodiments of the application have been described above by means of functional building blocks, which illustrate the implementation of certain functionality, and relationship of functional building blocks to one another and to the overall system. The boundaries of these functional building blocks have been arbitrarily defined herein for the convenience of the description. Alternative boundaries can be defined so long as the specified functionality and relationships of these building blocks are maintained.

[0150] The above description of the specific embodiments is merely illustrative of the general principles of the application. Other arrangements will be apparent to those skilled in the art upon reading the present specification, the embodiments being illustrative and not restrictive. Modifications can be made to the embodiments and other implementations of the subject application without departing from its scope, and the generic principles herein can be applied to other implementations.

[0151] The breadth and scope of the present application should not be limited to any of the above-described exemplary embodiments, but should be defined in accordance with the following claims and their equivalents.

Claims

1. A method for fluid transfer, comprising: laterally translating a transfer module within an interior of a housing to align structures on an outer surface of the transfer module with a first port associated with a first chamber and a second port associated with a second chamber, wherein the housing includes the first chamber and the second chamber; aspirating a sample from the first chamber to the second chamber via at least the structures aligned on the first port and the second port; and aspirating a sample from the second chamber to a third chamber located within the transfer module via a port through a wall of the transfer module.

2. The method of claim 1, further comprising mixing a sample introduced into the first chamber with a buffer disposed in the first chamber.

3. The method of claim 1, further comprising mixing a sample aspirated into the third chamber with a liquid already present in the third chamber.

4. The method of claim 1, further comprising introducing a sample into the first chamber with a swab carrying the sample.

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