RELATED APPLICATION

[0001] T his patent application claims priority to United States provisional patent application number 63/128,198, which was filed on December 21, 2020, and which is incorporated herein by reference for all purposes.

FIELD

[0002] The present arrangements and teachings relate to portable and hand-held detection devices, and methods relating thereto, for testing samples containing a target analyte (e.g., viruses such as severe acute respiratory syndrome SARS-CoV-2 (“COVID-19”) virus, harmful bacteria and chemical constituents of interest, and/or RNA, DNA, and/or protein for purposes of species identification). More specifically, the present arrangements and teachings relate to a device, and methods relating thereto, that use novel opening, closing, and compression mechanisms and features, for sealing off removable cartridges that are used to test for presence and/or characteristics of a target analyte in a biological sample.

BACKGROUND

[0003] Testing samples containing one or more target analytes, and in particular, biological samples with one more target nucleic acids, has been a staple of biology laboratories for many decades. The advent of quantitative real-time PCR (qPCR) made the identification of and measurement of genetic targets accessible and practical for a greater number of analytical tests and applications. This allows for the presence and/or characteristics of a target to be monitored through a reaction driven by external thermal energy input (e.g., thermomechanical energy). A computer-controlled reaction chamber is used to precisely control the reaction temperature for a desired method. Optical sensors, placed in a separate detection chamber, are used to measure the signal emitted by target analytes during the reaction method.

[0004] Conventional systems and methods have been used in professional laboratory settings, wherein sample preparation and data analysis has been performed by experts trained to use sophisticated equipment in laboratory settings that also provide access to various storage conditions for reaction materials (e.g., refrigerators) to practice these systems and methods. Demands for diagnostic testing in resource-limited areas that do not have access to such laboratory settings and personnel, however, remain. Unfortunately, conventional systems and methods encounter difficulties in maintaining relatively closed reaction conditions when carrying out reactions, including but not limited to optical detection reactions, in the field.

[0005] What is, therefore, needed are systems and methods facilitate testing of target analytes without encountering the drawbacks associated with the conventional systems and methods of testing.

SUMMARY

[0006] To this end, the present arrangements and teachings offer different types of systems, and methods relating thereto, that allow an automated, sample- to- result methodology that may be performed by non-expert users and provide immediate results in the field. Specifically, the present arrangements and teachings offer, inside a hand-held detection device, provisions for sealing off’ reactions for tests that determine presence and/or characteristics of one or more target analytes (including but not limited to biological samples having one more target nucleic acids or proteins). The present arrangements and methods use removable cartridges that are configured to seal off reactions from ambient conditions, to prevent evaporation during thermal processing, and to maintain pressure for such reactions that provide immediate results in the field.

[0007] In one aspect, the present arrangements provides hand-held detection devices for seating off a removable cartridge. One such exemplar hand-held detection device includes a cartridge inlet designed to receive the cartridge and a cartridge stage coupled to or extending from the cartridge inlet and being designed to have secured therein the cartridge.

[0008] The exemplar hand-held detection device further includes a compression assembly disposed adjacent to the cartridge stage and includes a pressing surface. In an open state of the compression assembly, the pressing surface is released from a closed state and thereby displaces at least a portion of the compression assembly away from the cartridge stage, allowing a cartridge access through an unobstructed loading path to be secured on the cartridge stage. Upon receiving an external pressing force on the pressing surface, the compression assembly is designed to acquire a compressed state, in which the pressing surface displaces towards the cartridge stage and the compression assembly seals off the cartridge present inside the cartridge stage from an environment around the cartridge stage.

[0009] The exemplar hand-held detection device further still includes a switch that is communicatively coupled to the pressing surface of the compression assembly. In this configuration, upon receiving an external switching force, the switch places the pressing surface in the open state and the compression assembly is in a non-operational state. Further, when the pressing surface receives an external pressing force and is placed in a closed state, the pressing surface places the compression assembly in the compressed state or in an operational state.

[0010] In certain embodiments of the preferred arrangements, the switch further includes an engaging end coupled to a first horizontal spring and has defined therein a locking aperture. A protruding portion of a locking plate occupies the locking aperture.

[0011] Further, the cartridge stage may include a cartridge-receiving aperture for securing the removable cartridge. The cartridge-receiving aperture receives the cartridge containing the target analyte and when a compression module, as explained below in greater detail, of the compression assembly compresses against the cartridge, the cartridge-receiving aperture serves to stabilize and prevent displacement of the cartridge under compression.

[0012] The locking plate has preferably defined therein a central aperture and at least two guide-posting-engaging apertures. In this configuration, the central aperture is part of an optical pathway and is designed to allow for optical detection of a target analyte disposed inside the cartridge. The two guide-post-engaging apertures are disposed adjacent to the central aperture. Further, each of the guide-post-engaging apertures have passing therethrough a guide post that is connected to the pressing surface. By way of example, a first guide post passes through a first guide-post-engaging aperture and a second guide post passes through a second guide-post engaging aperture. [0013] In preferred implementations of these arrangements, the pressing surface is connected to at least two of the guide posts, each of which comprises a washer and a shaft. The washers are disposed at one end of the shafts and the shafts pass through the guide-post-engaging apertures.

In the open state of the pressing surface, presence of the washer prevents vertical displacement of the shaft beyond a position of the guide-post-engaging aperture such that the pressing surface remains coupled to the guide-post-engaging apertures of the locking plate during the open state of the pressing surface. In other words, the washer prevents the subassembly of the guide post and the compression assembly, including the pressing surface, from being disassembled from the other components of the hand-held detection device during the open state of the pressing surface. [0014] Continuing with these preferred implementations, the shaft may have substantially circumferentially defined thereon at least one groove such that, in the compressed state of the compression assembly, inner edges of each of the guide-post-engaging apertures engage with respective ones of the grooves to maintain the compressed state of the compression assembly. In other implementations, the shaft is not of cylindrical shape, and the groves are defined on the outer surface of the shaft to allow for engagement with guide-post-engaging apertures.

[0015] Each of the guide posts, preferably, have disposed therearound a bearing and a vertical spring. The vertical spring is disposed between the bearing and the pressing surface. In these preferred implementations, the bearings are designed to not vertically displace with vertical displacement of the guide posts. Rather, the bearings are designed to guide vertical displacement of the guide posts through the bearings. When the compression assembly transitions from the non-operational state to the operational state, the vertical springs undergo compression between the bearing and the pressing surface. When the compression assembly transitions from the operational state to the non-operational state, the vertical springs undergo decompression between the bearing and the pressing surface. Preferably, force supplied by such decompression of the vertical springs pushes the top surface of the compression assembly away from a cartridge. [0016] The hand-held detection device of the present arrangements may further include a switch frame disposed adjacent to the locking plate. The switch frame houses at least a portion of the switch therein. In this arrangement, the bearing and the vertical spring are disposed between the pressing surface and the switch frame. Further, the switch frame has preferably defined therein vertical displacement apertures through which the guide posts undergo vertical displacement as the compression assembly transitions between the non-operational state and the operational state. Such vertical displacement apertures may also be part of an optical pathway designed to allow for optical detection of a target analyte disposed inside a cartridge.

[0017] In the operational state of the compression assembly, the inner edges of guide-post- engaging apertures engage with the grooves defined on the guide posts to prevent vertical displacement of the guide posts. In this operational state, the vertical springs operate to spring load the respective one of the guide posts. When the compression assembly transitions from the operational state to the non-operational state, the inner edges of the guide-post-engaging apertures undergo disengagement from the grooves and allowing vertical displacement of the guide posts. Further, during the transition from the operational state to the non-operational state, the vertical springs undergo decompression, springing forward towards the pressing surface, thereby pushing the pressing surface away from the cartridge stage, and thereby forcing the pressing surface to acquire an open state.

[0018] When the compression assembly transitions from the operational state to the non- operational state, the switch undergoes displacement such that the locking aperture of the switch displaces the protruding portion of the locking plate. In one embodiment of the present arrangements, displacement of the protruding portion of the locking plate disengages inner edges of the guide-post-engaging apertures from the grooves of the guide posts.

[0019] The above-mentioned switch frame may house the first horizontal spring, which is coupled to the switch. In tins configuration, when the switch receives the external switching force and is displaced from its original position to a new position, the engaging end of the switch causes spring loading of the first horizontal spring and almost contemporaneously, causes displacement of the locking aperture, which in turn causes displacement of the protruding portion, which in turn disengages the inner edges of the guide-post-engaging apertures from the grooves. The present teachings recognize that the switch in these arrangements, upon cessation of the external switching force, is designed to return from the new position to the original position under a spring unloading action of the first horizontal spring.

[0020] The switch frame preferably houses a second horizontal spring that engages with a spring engaging end of the locking plate such that in the compressed state of the compression assembly, a spring loading action of the second horizontal spring maintains engagement of the guide-post-engaging apertures of the locking plate with the grooves. In the open state of the pressing surface or the non-operational state of the compression assembly, the spring loading action of the second horizontal spring maintains engagement of the guide-post-engaging apertures with an outer surface of the shafts.

[0021] In this open state, the guide-post-engaging apertures are not engaged with the grooves of the shaft, but are contacting and/or engaged with a non-grooved portion of the shaft such that upon receiving the external pressing force at the pressing surface, the grooves of the shaft (of the guide posts) vertically displace towards the locking plate until the grooves engage with inner edge of the guide-post-engaging apertures of the locking plate. As a result, the spring loading action of the second horizontal spring forces engagement of the grooves with inner edges of the guide-post-engaging apertures.

[0022] In certain preferred embodiments of the present hand-held devices, the compression assembly includes a compression module and a retractable housing including the pressing surface. The retractable housing is coupled to and houses at least a portion of the compression module such that upon receiving the external pressing force on the pressing surface, the compression module acquires the compressed state, in which the compression module seals off the cartridge present inside the cartridge stage. The guide posts are housed inside the retractable housing.

[0023] These preferred embodiments further include an ingress seal coupled to the retractable housing such that when the compression assembly is in the compressed state, the ingress seal operates in conjunction with the cartridge stage to seal off access through the cartridge stage.

[0024] In another aspect, the present teachings offer methods for detecting a target analyte. One such exemplar method includes obtaining a hand-held target-analyte detection device and a cartridge containing a target analyte. The hand-held target-analyte detection device includes a switch, a compression assembly, a cartridge stage, and a cartridge inlet.

[0025] Next, the exemplar detecting method proceeds to activating the switch and placing the compression assembly in a non-operational state. In this non-operational state, a pressing surface of the compression assembly is released, displacing away from the cartridge stage and thereby providing an unobstructed loading path for the cartridge to be secured inside the cartridge stage. In other words, in an open state of the pressing surface, the compression assembly is non-operational and therefore in a non-operational state.

[0026] The exemplar detecting method then includes loading the cartridge through the cartridge inlet and receiving the cartridge inside the cartridge stage to form a loaded cartridge stage.

[0027] Then, the exemplar detecting method involves pressing the pressing surface of the compression assembly towards the loaded cartridge stage and thereby sealing off access through the cartridge stage. As a result, the pressing step provides a relatively closed environment, protecting the cartridge and/or other internal components of the device from the environment outside of the device.

[0028] In those embodiments of the present arrangements where the compression assembly includes or is coupled to an ingress seal, the above-mentioned pressing step includes forcing the ingress seal towards the cartridge stage to seal off access through the cartridge stage. This also may protect the cartridge and/or other internal components of the device from the environment outside of the device,

[0029] In yet another aspect, the present teachings provide methods for assembling handheld detection devices of different arrangements. One such exemplar method includes obtaining a compression assembly having at pressing surface and at least two guide posts. In this configuration of the compression assembly, the guide posts are coupled to the pressing surface and the guide posts include a shaft and washer.

[0030] T he exemplar assembling method then involves assembling a locking plate including at least two guide-post-engaging apertures and a switch frame. The switch frame includes at least two vertical displacement apertures such that at least two of the guide-post-engaging apertures and at least two of the vertical displacement apertures are aligned to allow vertical displacement of the shafts.

[0031] Next, the exemplar assembling method includes passing at least two terminating ends of at least two of the guide posts through at least two of the guide-post-engaging apertures and at least two of the vertical displacement apertures.

[0032] The exemplar assembling method may finally conclude with a step that involves installing at least two washers on at least two of the terminating ends to secure at least two of the guide-post-engaging apertures and at least two of the vertical displacement apertures within at least two of the shafts,

[0033] The construction and method of operation of the present arrangement and present teachings, however, together with additional objects and advantages thereof, will be best understood from the following descriptions of specific embodiments when read in connection with the accompanying figures that described below.

BRIEF DESCRIPTIONS OF THE DRAWINGS

[0034] Figure 1 shows a perspective view of a hand-held detection device, according to one embodiment of the present arrangements, and a cartridge containing a target analyte that undergoes detection in the hand-held detection device.

[0035] Figure 2A shows a perspective view of a cartridge inlet and a compression assembly porti ons, according to one preferred embodiment of the present arrangements, of the hand-held detection device of Figure 1. [0036] Figure 2B shows a perspective view of the cartridge inlet and the compression assembly portions of Figure 2A and shows a pressing surface of the compression assembly in an open state.

[0037] Figure 2C shows a perspective view of the cartridge inlet and the compression assembly portions of Figure 2 A and shows the cartridge shown in Figures 1 , 2A, and 2B loaded into the cartridge inlet of Figures 1, 2A, and 2B with the compression assembly in a compressed and operational state and the pressing surface in a closed state.

[0038] Figure 3 A shows a side-sectional view of a certain salient components of the handheld detection device, according to one embodiment of the present arrangements, with a cartridge, disposed on a cartridge card and prior to being loading inside the hand-held detection device.

[0039] Figure 3B shows a side-sectional view' of salient components of the hand-held detection device of Figure 3 A, except the cartridge is loaded inside the hand-held detection device.

[0040] Figure 4A shows a perspective view of certain salient components of a compression module, according to one embodiment of the present arrangements, shown in a compressed state or an operational state, but in the absence of a cartridge (not shown to simplify illustration).

[0041] Figure 4B shows a perspective view of certain salient components of a compression module of Figure 4A, except the compression module is in a non-operational state in the absence of a cartridge (not shown to simplify illustration).

[0042] Figure 5A shows a partial cutaway view of certain salient components of the handheld detection device of Figure 4B, including a portion of the compression assembly in the non- operational state having a pressing surface in an open state.

[0043] Figure 5B shows a partial cutaway view of certain salient components of the handheld detection device of Figure 5 A, including the compression assembly in an operational state where the pressing surface in a closed state after receiving an external pressing force. [0044] Figure 6 shows a process flow diagram, according one embodiment of the present teachings, for detecting a target analyte contained in a sample loaded on the cartridge shown in Figures 1, 2 A and 2B.

[0045] Figure 7 shows a process flow diagram, according one embodiment of the present teachings, for assembling the hand-held detection device shown in Figures 1, 2A, 2B, 2C, 3 A, 3B, 4A, 4B, 5A, and 5B. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0046] In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present arrangements and teachings. It will be apparent, however, to one skilled in the art that the present teachings may be practiced without limitation to some or all of these specific details. In other instances, well-known method steps have not been described in detail in order to not unnecessarily obscure the present arrangements and teachings.

[0047] The systems and methods of the present inventions use or provide a simple, integrated method and a portable, hand-held detection device for performing and facilitating reactions involving a target analyte (e.g., determining presence or characteristics of a target analyte, such as by way of non-limiting example, DNA, RNA, or protein). The hand-held target-analyte detection device allow for reactions performed inside a removable cartridge having one more target analytes disposed therein. A cartridge may be thought of as a structure or combination of structures for carrying out one or more such reactions (e.g., in one or more reaction wells disposed within the cartridge). Use of such removable cartridges provides certain advantages, including the convenience of pre-loading cartridges in a laboratory setting with reagents, buffers, probes, and other materials used for target-analyte testing, such that a user in the field, where a target analyte is collected, may carry out target-analyte testing in the field with loading of such components into or on a cartridge carried out previously, in a laboratory setting, and/or by more technically trained mvdivduals. Such cartridges may be comprised of optically translucent material such that the contents and reactions therein are monitored by optical detection carried out in such devices.

[0048] The present teachings, however, recognize that reactions carried out using such cartridges may be inaccurate, unreliable, and/or inconsistent, insofar as cartridges may not maintain relatively closed conditions during a target-analyte rection, such that the reaction is not sealed off from ambient conditions, evaporation may occur, and/or pressure and/or temperature levels may be difficult to maintain. Accordingly, the sy stems and methods of the present arrangements and teachings provide the advantage of sealing off such cartridges during reactions in a target-analyte detecting device so as to maintain a relatively closed environment during such reactions. Preferably, such cartridges are comprised of compressible material to facilitate their compression using the systems and methods of the present teachings.

[0049] Such sealing and compression may prevent ingress or egress into or out of the cartridge (e.g., at or near regions where components may be loaded into a cartridge; or at regions where discrete cartridge components are coupled or engaged), thus maintain a relatively closed environment for reactions inside of a cartrdige. By way of example, a cartridge may contain a base portion that is loaded and a cap portion that is then secured on the cap portion after loading; a target-analyte detection reaction performed inside the cartridge may supply pressure forces that cause “leaks” of moisture or other matter from the cartridge, e.g., in areas where the cap portion and base portion of an exemplar cartridge are coupled together, or in a loading area on the cartridge. The present teachings recognize, however, that providing compressive force on the cartridge during such reactions facilitates maintaining a relatively closed environment for the reaction.

[0050] In one aspect, the present arrangements and teachings disclose a hand-held detection device for sealing off a removable cartridge. The hand-held detection device preferably includes several key components. For example, the hand-held detection device includes a cartridge inlet designed to receive the cartridge within hand-held devices of the present teachings and arrangements. [0051] As another example, the hand-held detection device includes a cartridge stage that is coupled to or extending from the cartridge inlet, such that the cartridge stage is designed to have the cartridge secured therein or thereon.

[0052] As another example, the hand-held detection devices of the present teachings and arrangements include a compression assembly, which has a pressing surface disposed adjacent to a cartridge stage. According to one embodiment of the present arrangements, a compression assembly is in a “non-operational state,” before the cartridge is loaded inside the device. In this non-operational state, the compression assembly is displaced away from the cartridge stage, which provides a cartridge access through a cartridge inlet and along an unobstructed loading path within the device for the cartridge to be secured in or on the cartridge stage. In this non- operational state of the compression assembly, the pressing surface of the compression device is open and therefore deemed to be in an “open state.”

[0053] According to another embodiment of the present arrangements, however, a compression assembly is in a “compression state,” such that the compression assembly compresses a cartridge secured in a cartridge stage. This compressed state is also known as an operational state of the compression assembly. Preferably, the transformation from a non- operational state to an operational state of the compression assembly is facilitated by an external pressing force being applied to the pressing surface of the compression assembly. When an external force is received at the pressing surface, the pressing surface displaces towards a cartridge stage, placing the compression assembly in a compression state to seal off the cartridge present inside the cartridge stage from an environment around the cartridge stage. This “compression state” of a compression assembly may also be thought of as a an “operational” state of the compression assembly, insofar as a target analyte inside a cartridge preferably undergoes a target-analyte-detection reaction while the cartridge is being compressed by the compression assembly during this compressed state,

[0054] Hand-held devices of the present arrangements and teachings also include a switch that is communicatively coupled to a pressing surface of a compression assembly such that when the switch receives an external switching force, the switch places the pressing surface in an open state and the compression assembly in a n on-operational state, and when the pressing surface receives an external pressing force to acquire a closed state, the pressing surface places the compression assembly in a compressed or state. In certain embodiments of the present arrangements, a switch is mechanically coupled to a pressing surface of a compression assembly. In other embodiments of the present arrangements, however, a switch is electrically, magnetically, and/or digitally coupled to a pressing surface.

[0055] Figure 1 shows some of these salient features of a system 100, according to one preferred embodiment of the present arrangements, for detecting a target analyte. System 100 includes a handheld detection device 102 for sealing off a removable cartridge 106 containing the target analyte. Hand-held detection device 102 includes a compression assembly 104 with a pressing surface 105, a cartridge inlet 110, and a switch 112, Cartridge 106 is secured on a cartridge card 108.

[0056] Cartridge 106 is preferably comprised of optically translucent material that provides an optical pathway therethrough during optical detection reactions carried out in the cartridge. Cartridge 106 is also preferably comprised of compressible material to facilitate its compression using the systems and methods of the present teachings so as to seal off the cartridge during reactions, including optical detection reactions, carried out in such cartridges using the present devices.

[0057] Cartridge card 108 is an optional feature that facilitates handling and transfer of cartridge 106 into and out of the devices of the present arrangements and teaching by providing a handling surface.

[0058] Figures 2A-2C shows a compression assembly, e.g., compression assembly 104 of Figure 1, at different states, according to preferred embodiments of the present teachings and arrangements, /.<?., at a “storage state” of a hand-held detection device 202 (Figure 2A), at an open state, or a non-operational state, of a compression assembly 204’ of a device 202’ (Figure 2B), and at a compressed state, or an operational state, of a compression assembly 204” of a device 202” (Figure 2C).

[0059] In Figure 2A, device 202, a compression assembly 2.04, a pressing surface 205, a cartridge 206, a cartridge card 208, a cartridge inlet 210, and a switch 212, are the same as their counterparts in Figure I, i.e., device 102, compression assembly 104, pressing surface 105, cartridge 106, cartridge card 108, cartridge inlet 110, and switch 112, respectively.

[0060] Figure 2A shows hand-held detection device 202 in a storage state, according to one embodiment of the present arrangements. In the storage stage, hand-held detection device 202 is at an initial stage before the device goes into an operational state. Further, in storage stage, the compression assembly of hand-held detection device 202 is held in a compressed state so as to not allow' contaminants to enter hand-held detection device 202. Figure 2A also shows a. cartridge 206 disposed on a cartridge card 208 and placed outside hand-held device 202 before undergoing processing (e.g., detection of target analyte contained inside cartridge 206).

[0061] Specifically, by pressing surface 205 having a closed state, access through a cartridge stage is blocked through cartridge inlet 210 (explained in further detail below' with reference to ingress seal 322’ and cartridge stage 314’ of Figure 3B) and/or past pressing surface 205, which is in a closed state. In such manner, device 202 may be thought of as being in a “storage” stage, because the device is non-operational, and connection to an outside environment is blocked through cartridge inlet 210 by a closed state of pressing surface 2.05’ and/or past pressing surface 205, which is in a closed state, protecting internal components of device 202 during storage.

[0062] Figure 2B shows hand-held detection device 202’ in a non-operational state, according to one embodiment of the present arrangements, with a cartridge 2.06’ still outside of hand-held device 202’, but ready for loading inside hand-held detection device 202’. In Figure 2B, device 202’, a. compression assembly 204’, a pressing surface 205’, a. cartridge 206’, a cartridge card 208’, a cartridge inlet. 21 O’, and a switch 212, are substantially similar to their counterparts in Figure 2A, i.e., device 202, compression assembly 204, pressing surface 205, cartridge 206, a cartridge card 208, cartridge inlet. 210, and switch 212. Unlike with device 202 of Figure 2A, however, Figure 2B shows pressing surface 205’ in an open state, which provides an unobstructed loading path beyond cartridge inlet 210’ for cartridge 206’ to be secured on a cartridge stage inside device 202’.

[0063] As explained in further detail below with reference to Figures 4A-4B, transformation of pressing surface 205’ from a closed state to an open state is triggered by switch 212’, which is communicatively coupled to pressing surface 205’ of compression assembly 204’, such that upon receiving an external switching force, switch 212’ places pressing surface 205’ in an open state and compression assembly 204’ is maintained in a non-operational state, without having cartridge 206’ present therein.

[0064] Figure 2C shows hand-held device 202”, according to one embodiment of the present arrangements, with a cartridge (not shown to simplify illustration) being compressed therein. In Figure 2C, device 202”, compression assembly 204”, a pressing surface 205”, a cartridge card 208’, a cartridge inlet 210”, and a switch 212”, are substantially similar to their counterparts in Figure 2B, i.e., device 202’, compression assembly 204’, pressing surface 20”, cartridge card 208, cartridge inlet 210’, and switch 212’.

[0065] As shown in the embodiment of Figure 2C, compression assembly 204” is in a compressed state, and pressing surface 205” is in a closed state, with a cartridge (not visible in Figure 2C) secured within device 202”. Preferably, transformation of a compression assembly from a non-operational state (as shown by compression assembly 204’ of Figure 2B) to a compression state (as shown by compression assembly 204” of Figure 2C) is achieved by applying an external pressing force on pressing surface 205” such that components of the compressing assembly that are directly and indirectly connected to pressing surface 205” are displaced towards a cartridge stage (e.g., cartridge stage 314’ of Figure 3B), and such that compression assembly 204” seals off a cartridge secured inside a cartridge stage (not visible in Figure 2C) from an environment around the cartridge stage.

[0066] Figure 3A is a side-sectional view of a hand-held device 302, according to one embodiment of the present arrangement, and a removable cartridge 306 disposed on a cartridge card 308 outside of device 302. Figure 3 A shows salient components of compression assembly 304 disposed inside device 302 and involved in sealing off removable cartridge 306. To this end. Figure 3A shows device 302 having a compression assembly 304 that includes a pressing surface

305, a retractable housing 318, a compression module 320, and an ingress seal 322; and a cartridge inlet 310 leading to a cartridge stage 314 with a cartridge- receiving aperture 316 as part of the cartridge stage. Device 302, compression assembly 304, pressing surface 305, cartridge

306, cartridge card 308, and a cartridge inlet 310, are substantially similar to their counterparts in Figure 2B, i.e., device 202’, compression assembly 204’, pressing surface 205’, cartridge card 206’, cartridge 208’, and cartridge inlet 210’. As with the embodiment of Figure 2B, Figure 3A shows compression assembly 304 in a non-operational state with pressing surface 305 in an open state.

[0067] According to one preferred embodiment of the present arrangements, compression assembly 304 includes retractable housing 318 (which includes pressing surface 305) and compression module 320. Preferably, retractable housing 318 is coupled to and houses at least a portion of compression module 320 such that upon pressing surface 305 receiving an external pressing force, compression module 320 will acquire a compressed state in which compression module 320 seals off a cartridge present in cartridge stage 314 (as shown in Figure 3B). In other words, compression module 320 seals off a cartridge by compressing the cartridge, preferably against a cartridge stage, and preferably during target-analyte detection reactions processed in the cartridge.

[0068] To this end, Figure 3B is a side-sectional view' showing certain internal components of a system 300’ for sealing off a removable cartridge, with a compression assembly 304’ of device 302’ in a “closed” or “compressed” state, according to one embodiment of the present arrangements. In Figure 3B, system 300’, a device 302’, a compression assembly 304’, a pressing surface 305’, a cartridge card 306’, a cartridge 308’, a cartridge inlet 310’, a cartridge stage 314’, a cartridge-receiving aperture 316’, a retractable housing 318’, a compression module 320’, and an ingress seal 322’, are substantially similar to their counterparts in Figure 3 A, i.e., system 300, device 302, compression assembly 304, pressing surface 305, cartridge card 306, cartridge 308, cartridge inlet 310, cartridge stage 314, cartridge-receiving aperture 316, retractable housing 318, compression module 320, and ingress seal 322.

[0069] As shown in in the embodiment of Figure 3B, cartridge 306’ is secured in cartridge aperture 316’, which is a part of cartridge stage 314’. In other embodiments of the present arrangements, however, cartridge aperture 316’ is not used and cartridge 306’ is secured by other means to cartridge stage 314’.

[0070] Compression module 320’ of compression assembly 304’ is shown compressing, and as result, sealing off, cartridge 306’.

[0071] As shown in Figure 3B, ingress seal 322’, in conjunction with cartridge stage 314’, seals off access through cartridge stage 314’. Preferably, ingress seal 322’ is comprised of compressible material sufficient to seal access through cartridge state 314’ when ingress seal 322’ presses against an uneven or soft surface. Use of ingress seal 322’ provides the advantage of sealing interior components of device 302’, including cartridge 306’, from ambient conditions and from particles such as dust or debris that may interfere with reactions carried out in cartridge 306’, or that may otherwise disrupt or damage other internal components of device 302.’.

[0072] Figures 4A shows a perspective view (viewed from a side opposite to pressing surface, e.g., pressing surface 105 of Figure 1) of salient components, according to one preferred embodiment of the present arrangements, of a hand-held detection device 402 and that are used to transform a compression assembly 404 inside device 402 between a non-operational and an operational or a compressed state. Figure 4A includes a switch 412 (which is substantially similar to its counterpart in Figure 1, i.e., swatch 112) having a locking aperture 426 and an engaging end 428; a locking plate 430 having a central aperture 431, guide-post-engaging apertures 432a and 432b disposed on opposite ends of locking plate 430, a protruding portion 434 engaged with locking aperture 426, and a spring-engaging end 436; guide posts 438a and 438b (extending through apertures 432a and 432b, respectively), having washers 440a and 440b, grooves 442a and 442b, and shafts 444a and 444b, respectively, and bearings 452a and 452b disposed thereon, respectively; and a switch frame 450 coupled to switch 412 and locking plate 430 and having disposed thereon a first horizontal spring 446 engaged with engaging end 428 and a second horizontal spring 448 engaging with spring-engaging end 436. Figure 4A also shows a compression assembly 404. According to the embodiment of Figure 4A, device 402 and compression assembly 404 are in a compressed, or operational, state. In the perspective shown in Figure 4A, hatches show the region of compression assembly 404 that contacts or compresses a cartridge during an operational state of compression assembly 404. Preferably, the region of compression assembly 404 that compresses a cartridge (e.g., cartridge 306’ of Figure 3B) is part of a compression module (e.g., compression module 320’ of Figure 3B).

[0073] Switch 412 has an engaging end coupled to first horizontal spring 446 and has defined therein a locking aperture occupied by protruding portion 434 of locking plate 430, which is communicatively coupled to a pressing surface of device 402 (e.g., pressing surface 305’ of Figure 3B). According to the embodiment of Figure 4B, an external switching force may be applied to switch 412 towards first horizontal spring 446 such that switch 412 undergoes displacement, causing locking aperture 426 of switch 412 to displace protruding portion 434 of locking plate 430, which in turn disengages inner edges of guide-post-engaging apertures 432a and 432b from grooves 442a and 442b, respectively, to transform compression assembly 404 of Figure 4A to a non-operational state (as shown in Figure 4B).

[0074] First horizontal spring 446 (and second horizontal spring 448) are considered “horizontal” relative to a plane that is parallel to a cartridge stage of the cartridge secured inside device 402 (not shown in Figure 4A).

[0075] Guide-post-engaging apertures 432a and 432b each have passing therethrough guide posts 438a and 438b, respectively. Preferably, guide posts 438a and 438b are connected to a pressing surface of device 402 (e.g., pressing surface 305’ of Figure 3B), which is not visible in Figure 4 A.

[0076] As shown in the embodiment of Figure 4A, shafts 448a and 448b of guide posts 438a and 438b, respectively, each has substantially circumferentially defined thereon grooves 442a and 442b, respectively. In turn, inner edges of guide-post-engaging apertures 432a and 432b, respectively, engage with grooves 442a and 442b, respectively, to maintain the compressed state of compression assembly 404, as shown in Figure 4A.

[0077] Each of shafts 444a and 444b has secured thereon bearings 452a and 452b, respectively, and a vertical spring disposed therearound (not visible in Figure 4A), which is disposed between bearings 452a and 452b and a pressing surface of Figure 4A (as shown with reference to vertical springs 554a and 554b in Figure 5A). Preferably, bearings 452a and 452b are designed not to vertically displace with vertical displacement of guide posts 438a and 438b, respectively. In other words, bearings 452a and 452b are fixed relative to guide posts 438a and 438b, and are configured such that bearings 452a and 452b are designed to guide vertical displacement of guide posts 438a and 438b, respectively, during transformation between non- operational and operational states of compression assembly 404. As compression assembly 404 shown in Figure 4A acquires an operational state, vertical springs undergo compression between bearing 452a and 452b and a pressing surface (as shown with reference to vertical springs 554a’ and 554b’ and pressing surface 505’ in Figure 5A).

[0078] Switch frame 450 is disposed adjacent to locking plate 430 and preferably houses at least a portion of switch 412, and bearings 452a and 452b. Swatch frame 450 also includes vertical displacement apertures (not identified in Figure 4A to simplify illustration) through which guide posts 438a and 438b undergo vertical displacement as compression assembly 404 transitions between a non- operational state and an operational state.

[0079] As shown in the operational state of compression assembly 404 in Figure 4A, inner edges of apertures 432a and 432b engage with grooves 442a and 442b, respectively, to prevent vertical displacement of the guide posts. In other words, engagement between apertures 432a and 432b and grooves 442a and 442b, respectively, maintain device 402 and compression assembly 404 in a compression state. To this end, vertical springs on guideposts 432a and 432b operate to spring load each of guide posts 432a and 432b, respectively. In other words, the vertical springs are spring loaded, but they are prevented from driving vertical displacement of guide posts 432a and 432b by engagement of locking plate apertures 432a and 432b with grooves 442a and 442b. respectively.

[0080] Switch frame 450 also houses second horizontal spring 448, which engages with spring-engaging end 436 of locking plate 430. In the compressed state of compression assembly- 404, a spring loading action of second horizontal spring 448 maintains engagement of guide- post-engaging apertures 432a and 432b with grooves 442a and 442b, respectively. In other words, during a compression state of device 402 and compression assembly 404, spring loading of second horizontal spring 448 (which may be considered horizontal relative to a plane parallel to a cartridge stage) provides force sufficient to maintain engagement of grooves 442a and 442b with guide-post-engaging apertures 432a and 432b, respectively .

[0081] Upon receiving incidental pressing forces or contact at any surface of device 402, including pressing surface 405, such as when device 403 is accidentally dropped, the present arrangements prevent device 402 from transitioning from an operational state to a non- operational state. Specifically, upon receiving such incidental pressing force, the inner edges of the guide-post-engaging apertures do not disengage from the grooves of the shaft of the guide posts. To this end, Figure 4A shows a gap (denoted by location “A”) defined in locking aperture to tolerate such incidental pressing forces or contact.

[0082] Central aperture 431 of locking plate 430 is preferably part of an optical pathway- designed to allow for optical detection of a target analyte disposed inside a cartridge (e.g, cartridge 306’ of Figure 3B).

[0083] Figure 4B shows a perspective view' of salient components, according to one embodiment of the present arrangements, used to transform a compression assembly between an operational state to a non-operational state. Device 402’ is the same as device 402 of Figure 4A, except compression assembly 404’ of device 402’ is shown in a non-operational state.

[0084] In Figure 4B, device 402’, a switch 412’, compression assembly 404’, a locking aperture 426’, an engaging end 428’, a locking plate 430’, a central aperture 431 ’, guide-post- engaging apertures 432a’ and 432b’, a protruding portion 434’, a spring-engaging end 436’, guide posts 438a’ and 438b’, washers 440a’ and 440b’, grooves 442a’ and 442b’, shafts 444a’ and 444b’, a first horizontal spring 446’, a second horizontal spring 448’, a switch frame 450’, and bearings 452a’ and 452b’, are substantially similar to their counterparts in Figure 4A, i.e., device 402, switch 412, compression assembly 404, locking aperture 426, engaging end 428; locking plate 430, central aperture 431, guide-post-engaging apertures 432a and 432b, protruding portion 434, spring-engaging end 436, guide posts 438a and 438b, washers 440a and 440b, grooves 442a and 442b, shafts 444a and 444b, first horizontal spring 446, second horizontal spring 448, a switch frame 450, and bearings 452a and 452b.

[0085] According to the embodiment of Figure 4B, switch 412’, upon receiving an external switching force, places a pressing surface (not visible in Figure 4B) in an open state and compression assembly 404’ in a non-operational state.

[0086] Preferably, switch 412’ is designed to return from a new position (i.e., when a switching force is applied) to an original position under a spring unloading action of first horizontal spring 446’ upon cessation of the external switching force.

[0087] As shown in Figure 4B, inner edges of guide-post-engaging apertures 432a’ and 432b’ have undergone disengagement from grooves (e.g., grooves 442a and 442b of Figure 4A), allowing vertical displacement of guide posts 438a’ and 438b’, and vertical springs undergo decompression, springing a pressing surface to acquire an open state,

[0088] In a similar manner, when a pressing surface is released from closed state to an open state, at least a portion of compression assembly 404’ is displaced away from a cartridge stage (not shown in Figure 4B), allowing a cartridge access through an unobstructed loading path to be secured on the cartridge stage. To this end, compression assembly 404’ of Figure 4B is shown displaced away a cartridge stage (which is disposed adjacent to locking plate 430’) relative to a location of compression assembly 404 of Figure 4A.

[0089] Likewise, though pressing surfaces are not visible in Figures 4A and 4B, Figure 4A shows an open state of a pressing surface on compression assembly 4A (e.g., pressing surface 305 of Figure 3 A) and Figure 4B shows a closed state of a pressing surface on compression assembly 4B (e.g,, pressing surface 305’ of Figure 3B).

[0090] As shown in Figure 4B, a spring loading action of second horizontal spring 448’ maintains engagement of guide-post-engaging apertures with shafts on guideposts 438a’ and 438b’.

[0091] Figure 5A is a cross-sectional view of certain salient components of a hand-held analyte-detection device 502, according to one embodiment of the present arrangements, for transforming a compression assembly 504 between operational and non-operational states. Figure 5A shows device 502 with a pressing surface 505 in a closed state, according to one embodiment of the present arrangements. Figure 5B includes device 502, a compression assembly 504, pressing surface 505, a switch 512, compressing assembly 504, a locking plate 530 with guide-post engaging apertures 532a and 532b, guideposts 538a and 538b, grooves 542a and 542b, a second horizontal spring 548, bearings 552a and 552b, and a washer 544a, which are substantially similar to their counterparts in Figure 4B, i.e., device 402’, switch 412’, compression assembly 404’, locking plate 430’ with guide-post engaging apertures 432a’ and 432b’, guideposts 438a’ and 438b’, grooves 442a’ and 552b’, bearings 452a’ and 452b’, second horizontal spring 448’, and washer 440a’. Figure 5A also shows a pressing surface 505 and a cartridge inlet 510, which are substantially similar to their counterparts in Figure 2B, i.e., pressing surface 205’ and cartridge inlet 210’. Figure 5A also shows vertical springs 554a and 554b disposed between bearings 552a and 552b, respectively, and pressing surface 505.

[0092] Figure 5B shows the device of Figure 5 A with a pressing surface 505’ in a closed state, according to one embodiment of the present arrangements. Figure 5B includes a device 502’, a switch 512’, a compression assembly 504’ with a pressing surface 505’, a cartridge inlet 51 O’, a locking plate 530’ with guide-post engaging apertures 532a’ and 532b’, guideposts 538a’ and 538b’, second horizontal spring 538’, grooves 542a’ and 542b’, bearings 552a’ and 552b’, vertical springs 554a’ and 554b’, and a washer 544a’, which are substantially similar to their counterparts in Figure 5 A, i.e., device 502, switch 512, compression assembly 504 with pressing surface 505, cartridge inlet 510, locking plate 530 with guide-post engaging apertures 532a and 532b, guideposts 538a and 538b, grooves 442a and 552b, second horizontal spring 538, bearings 552a and 552b, vertical springs 554a and 554b, and washer 544a.

[0093] As shown in Figures 5 A and 5B, pressing surface 505 and 505’, respectively, are connected to guide posts 538a and 538b (Figure 5A) and 538a’ and 538b’ (Figure B), respectively, with each of the guide posts comprising a washer (e.g., washer 440a of Figure 5A and washer 440a’ of Figure 5b, respectively) disposed at one end of the shafts on the guideposts (e.g., the shaft of guide post 538a of Figure 5A and the shaft of guide post 538a’ of Figure 5B). As shown in the open state of pressing surface 505’ of Figure 5B, presence of washer 440a prevents vertical displacement of a shaft on guide post 538a (e.g., shaft 444a of guide post 438a of Figure 4A) beyond a position of guide-post-engaging aperture 532a of locking plate 530, such that pressing surface 505 remains coupled to locking plate 530 when pressing surface 505 of device 502. is in an open state. In certain embodiments of the present arrangements, such prevention of displacement of guidepost 538a by washer 540a prevents compression assembly 504 and guide posts 548a and 548b from being detached or separated from other components of device 502.

[0094] In preferred embodiments of the present arrangements, each of guide posts 538a and 538b have disposed therearound bearings 552a and 552b and vertical springs 554a and 554b, respectively, each of which vertical spring is disposed between bearing 552a and 552b, respectively , and pressing surface 505.

[0095] Bearings 552a and 552b are designed not to vertically displace with vertical displacement of guide posts 538a and 538b, respectively. In other words, bearings 552a and 552b are fixed relative to guide posts 538a and 538b, respectively, and are configured to allow vertical displacement of guide posts 538a and 538b, respectively, when a compression assembly transitions from a non-operational state (as shown by compression assembly 504 of Figure 5A) to an operational state (as shown by compression assembly 504’ of Figure 5B). In certain embodiments of the present arrangements, bearings 552a and 552b are fixed by connection or coupling to features located on a switch frame (e.g., switch frame 450 of Figure 4A).

[0096] As shown in Figure 5B with reference to an operational state of compression assembly 504', vertical springs 554a’ and 554b’ undergo compression between bearings 552a’ and 552b’, respectively, and pressing surface 505’. Likewise, as shown in Figure 5A, when compression assembly 504’ transitions to a non-operational state (as shown by compression assembly 504 of Figure 5 A), vertical springs 554a and 554b undergo decompression between bearings 552a and 552b, respectively, and pressing surface 504.

[0097] When compression assembly 504b is in an operational state, as shown in Figure 5B, inner edges of guide-post-engaging apertures 532a’ and 532b’, respectively, engage with grooves 542a’ and a groove defined on guide post 538b’ (not visible in Figure 5B), respectively, to prevent vertical displacement of guide posts 538a’ and 538b’, respectively, such that vertical springs 554a’ and 554b’ operate to spring load guide posts 538a’ and 538b’, respectively.

[0098] As shown in Figure 5B, when the compression assembly transitions to a non- operational state (as shown by compression assembly 505 of Figure 5 A), inner edges of guide- post-engaging apertures 532a and 532b undergo disengagement from grooves 542a and a grooved defined on guide post 538b (not visible in Figure 5A), allowing vertical displacement of guide posts 538a and 538b, as vertical springs 554a and 554b undergo decompression, springing pressing surface 505 to acquire an open state of the pressing surface.

[0099] Figure 6 shows a method 600, according to one embodiment of the present teachings, for detecting a target analyte. Method 600, preferably, beings with a step 602, which involves obtaining a hand-held target-analyte detection device and a cartridge containing a target analyte (e.g., device 102 and cartridge 106, respectively, of Figure I). The hand-held target-analyte detection device includes a switch (e.g., switch 1 12 of Figure 1), a compression assembly (e.g., compression assembly 104 of Figure 1), a cartridge stage (e.g., cartridge stage 314 of Figure 3 A), and a cartridge inlet (e.g., cartridge inlet 110 of Figure 1). [00100] Next, a step 604 includes activating the switch and placing the compression assembly in a non-operational state. In this non-operational state, a pressing surface of the compression assembly (e.g., pressing surface 205’ of Figure 2B) is released, displacing away from the cartridge stage and thereby providing an unobstructed loading path for the cartridge to be secured inside the cartridge stage. In other words, in an open state of the pressing surface, the compressional assembly is non-operational and therefore in a non-operational state.

[00101] Method 600 then proceeds to a step 606, which includes loading the cartridge through the cartridge inlet (e.g., cartridge inlet 110 of Figure 1) and receiving the cartridge inside the cartridge stage to form a loaded cartridge stage (e.g., as shown in Figure 3B with respect to cartridge 306’ and cartridge stage 314’).

[00102] Then, method 600 involves a step 606, which includes pressing the pressing surface of the compression assembly towards the loaded cartridge stage and thereby sealing off access through the cartridge stage. As a result, the pressing step provides a sealed environment for the target analyte inside the cartridge.

[00103] In those embodiments of the present arrangements where the compression assembly includes or is coupled to an ingress seal (e.g. ingress seal 32.2 of Figure 3A), the above- mentioned pressing step includes forcing the ingress seal towards the cartridge stage to seal off access through the cartridge stage (e.g., as shown in Figure 3B with respect to ingress seal 322’ and cartridge stage 314’).

[00104] Figure 7 shows a method 700, according to one embodiment of the present teachings, for assembling the hand-held detection devices of different present arrangements. Method 700 includes a step 702 of obtaining a compression assembly having at pressing surface and at least two guide posts (e.g., guide posts 438a and 438b of Figure 4 A). In this configuration of the compression assembly, the guide posts are coupled to the pressing surface and the guide posts include a shaft and washer (e.g., shafts 444a and 444b and washers 440a and 440b of Figure 4A).

[00105] Method 700 then involves an assembling step 704, which include assembling a locking plate (e.g., locking plate 430 of Figure 4A) including at least two guide-post-engaging apertures (e.g., guide-post-engaging apertures 432a and 432b of Figure 4A) and a switch frame (e.g., switch frame 450 of Figure 4A). The switch frame includes at least two vertical displacement apertures such that at least two of the guide-post-engaging apertures and at least two of the vertical displacement apertures are aligned to allow vertical displacement of the shafts.

[00106] Next, method 700 proceeds to a step 706, which includes passing at least two terminating ends of at least two of the guide posts through at least two of the guide-post- engaging apertures and at least two of the vertical displacement apertures.

[00107] Method 700 may conclude with a step 708, which involves installing at least two washers (e.g., washers 440a and 440b of Figure 4A) on at least two of the terminating ends to secure at least two of the guide-post-engaging apertures and at least two of the vertical displacement apertures within at least two of the shafts.

[00108] Although illustrative embodiments of the present arrangements and teachings have been shown and described, other modifications, changes, and substitutions are intended. Accordingly, it is appropriate that the appended claims be construed broadly and in a manner consistent with the scope of the disclosure, as set forth in the following claims.