Cartridge for lab-on-chip applications

Abstract

The present disclosure provides a cartridge for lab-on-chip applications. An example cartridge for lab-on-chip applications includes a first module including: at least one desiccant storage compartment; a dry reagent storage chamber; a fluid circuit fluidly connected to the dry reagent storage chamber; and a first air path connecting the dry reagent storage chamber to the desiccant storage chamber and including a film preventing liquid flow from the dry reagent storage chamber to the desiccant storage chamber. The cartridge also includes a second module including a container having an interior cavity for containing the liquid solution. The first module and the second module are adapted to be fluidly coupled to each other.

Description

[0001] Cross-reference to related applications

[0002] This application claims priority to Italian patent application No. 102024000020491, filed on September 13, 2024, entitled “CARTUCCIA PER APPLICAZIONILAB-ON-CHIP”, which is incorporated herein by reference in its entirety to the fullest extent permitted by law. Technical Field

[0003] This invention relates to cartridges for sample preparation and analysis of molecules. Specifically, this invention relates to the field of so-called Lab-On-Chip (LOC) devices, wherein a single cartridge comprises a structure designed to perform at least some steps of processing a sample to extract and analyze molecules. Background Technology

[0004] Lab-on-a-Chip (LOC) systems are known, particularly those relying on the use of cartridges (e.g., disposable cartridges) placed into a machine that typically performs analysis of the substances contained within the cartridge after pretreatment. Such systems are of vital importance to health, and their significance increases over time along with the number of analyses that can be performed simply by the patient alone or with the assistance of non-professionals.

[0005] Specifically, the aforementioned system enables the analysis of biomolecules such as nucleic acids, proteins, lipids, and polysaccharides. These analyses involve multiple steps starting from the raw materials (e.g., blood or saliva samples, or samples collected via nasal swabs (nasal samples)). These steps may include various degrees of sample pretreatment, lysis, purification, amplification, and analysis of the resulting products. The analytical methods vary depending on the target biomolecule to be analyzed or detected. Furthermore, the LOC system can also be used for the purification of non-biological samples (such as water samples) and the analysis of non-biological molecules.

[0006] The operations involved in sample processing and analysis require specific reagents. For example, nucleic acid analyses, such as those based on clustered regularly spaced short palindromic repeats (CRISPR), polymerase chain reaction (PCR), ligase chain reaction (LCR), strand displacement amplification (SDA), transcription-mediated amplification (TMA), rolling circle amplification (RCA), and loop-mediated isothermal amplification (LAMP), require specific enzymes to perform amplification and / or target recognition steps. As another example, in proteomics analyses such as enzyme-linked immunosorbent assays (ELISA), antibodies and enzymes suitable for selectively binding to the target analyte of interest are needed to perform the detection.

[0007] Reagents may be stored in liquid or solid form (e.g., lyophilized, freeze-dried, or dehydrated) depending on their properties. Reagents in solid form (hereinafter referred to as "dry reagents"), such as lyophilized enzymes in the case of CRISPR-based analyses, need to be stored in a dry environment to prevent unwanted hydration. In fact, the hydration of dry reagents must occur according to specific predetermined steps during sample analysis or pretreatment, depending on their function. Premature, unnecessary hydration can actually accelerate the degradation of dry reagents, thus shortening their shelf life.

[0008] One known solution to prevent premature hydration of the dried reagent involves storing it in a specific chamber created within a LOC (Liquid Oxide Canister) box. The LOC box is then sealed within an externally sealed container or package that holds a desiccant (e.g., a bag containing silica beads or silica gel) along with the box. The container may also be filled with a drying inert gas, such as nitrogen (N2) or argon (Ar).

[0009] The box is then stored in a sealed package with the desiccant throughout its shelf life until it is used. However, moisture may (accidentally) enter the package and permeate into the box, or moisture may have been present inside the box before, for example, the packaging process, causing the desiccant to hydrate and deteriorate.

[0010] Another possible cause of hydration and thus deterioration of the dried reagent can occur during early steps of the analysis to be performed. For example, in the CRISPR-based analysis described above, a lysis step is required to extract nucleic acids from cells present in a biological sample, which is typically diluted with an aqueous buffer. The lysis step can be performed by heating the biological sample in the presence of a specific reagent, thus causing partial evaporation of the aqueous buffer. The resulting vapors may then reach the dried reagent, hydrating it before its intended use and potentially degrading it.

[0011] Therefore, it is desirable to provide boxes that allow for more efficient and safe storage of dried reagents until they are used. Summary of the Invention

[0012] According to the present invention, a box for lab-on-a-chip applications is provided.

[0013] In one example embodiment, a box for lab-on-a-chip applications is provided. The box for lab-on-a-chip applications includes a first module and a second module. The first module includes: at least one desiccant storage chamber; a dry reagent storage chamber; a fluid circuit fluidly connected to the dry reagent storage chamber; a first air path connecting the dry reagent storage chamber to the at least one desiccant storage chamber and including a membrane that is impermeable to liquids but permeable to gases and vapors, the membrane being arranged in the first air path in a manner that prevents liquid flow from the dry reagent storage chamber to the at least one desiccant storage chamber; the second module includes a container having an internal cavity for containing a liquid solution; wherein the first module and the second module have corresponding first and second fluid connectors adapted to be fluidly coupled to each other; and wherein the first fluid connector of the first module is fluidly coupled to the fluid circuit, and the second fluid connector of the second module is fluidly coupled to the container.

[0014] In various embodiments, the cassette for lab-on-a-chip applications also includes one or more desiccants in at least one desiccant storage compartment and one or more dry reagents in a dry reagent storage compartment.

[0015] In various embodiments, the first module includes a first layer and a second layer coupled to each other; wherein the first air path includes: a first portion in the first layer fluidly connected to a desiccant storage chamber; a second portion in the second layer; a third portion in the first layer fluidly connected to at least one desiccant storage chamber; a first through hole extending through the first layer, fluidly connected to the first portion of the first air path and aerily coupled to the second portion of the first air path via a membrane; and a second through hole extending through the first layer, fluidly connected to the third portion of the first air path and aerily coupled to the second portion of the first air path via a membrane.

[0016] In various embodiments, the first module includes a first layer having a first face and a second face opposite to each other; wherein the first air path includes: a first portion at the first face of the first layer, the first portion being fluidly connected to a desiccant storage chamber; a second portion at the second face of the first layer; a third portion at the first face of the first layer, the third portion being fluidly connected to at least one desiccant storage chamber; a first through-hole extending from the first face through the first layer to the second face, the first through-hole being fluidly connected to the first portion of the first air path and coupled to the second portion of the first air path via air through a membrane; and a second through-hole extending from the first face through the first layer to the second face, the second through-hole being fluidly connected to the third portion of the first air path and coupled to the second portion of the first air path via air through a membrane.

[0017] In various embodiments, the first module includes a second layer and a third layer; wherein the second layer includes a tape or film coupled to a first side of the first layer, the tape or film being configured to seal a fluid circuit, at least one desiccant storage chamber, and a dry reagent storage chamber; and wherein the third layer includes at least one tape or film coupled to a second side of the first layer, and at least one heating element of semiconductor material coupled to the second side of the first layer.

[0018] In various embodiments, the first module and the second module have corresponding mechanical coupling means for mechanically coupling the first module to the second module.

[0019] In various embodiments, the first fluid connector and the second fluid connector are Luer connectors.

[0020] In various embodiments, the container is a sample collection container including a swab having a tip, a shaft coupled to the tip, and a cap coupled to the shaft; wherein the container has a threaded opening for inserting the swab into an internal cavity; wherein the cap of the swab is a threaded cap adapted to seal the internal cavity when the swab is inserted into the container and the threaded cap is screwed onto the threaded opening; and wherein the container includes a first portion of deformable material configured to undergo elastic deformation when internal pressure is applied.

[0021] In various embodiments, the container includes a second portion having a protrusion within an internal cavity such that when the swab is inserted into the container, the tip contacts the protrusion; and the second portion is configured to withstand the internal pressure without deformation.

[0022] In various embodiments, the second fluid connector includes a passing hole that passes through the container at the second portion, the elastic deformation being caused during use by pumping the liquid solution out of the container.

[0023] In various embodiments, the cassette for lab-on-a-chip applications also includes a second air path that connects at least one desiccant storage chamber to an outlet opening of the cassette via air. The outlet opening is configured to be connected to an external control unit for air suction.

[0024] In various embodiments, the cassette for lab-on-a-chip applications also includes a sealing layer coupled to the first module to seal the fluid circuit, at least one desiccant storage chamber, and a dry reagent storage chamber.

[0025] In various embodiments, the fluid circuit includes: a reaction chamber; a first fluid channel fluidly connecting a first fluid connector to the reaction chamber; and a second fluid channel fluidly connecting the reaction chamber to a dry reagent storage chamber. Attached Figure Description

[0026] To better understand the invention, some embodiments of the invention are now described by way of non-limiting example only with reference to the accompanying drawings, in which:

[0027] Figure 1 An embodiment of a lab-on-a-chip (LOC) system 1 according to an embodiment of the present invention is illustrated schematically;

[0028] Figure 2A A top view schematically illustrates fluid module A according to an embodiment of the present invention;

[0029] Figure 2B Fluid module A is schematically shown in the exploded view;

[0030] Figure 3A and Figure 3B This schematically illustrates the process during an exemplary analysis. Figure 2A The paths followed by air and liquid inside fluid module A;

[0031] Figure 4A A portion of the storage module B of box 2, including the swab container, is schematically shown;

[0032] Figure 4B The container for the swab was shown. Figure 4A swab container;

[0033] Figure 5A Different fluid module A and storage module B are shown according to embodiments of the present invention;

[0034] Figure 5B It shows Figure 5A Details of the mechanical connection between fluid module A and storage module B;

[0035] Figure 6 Another different fluid module A and storage module B are shown according to another embodiment of the present invention;

[0036] Figure 7 An exploded view of fluid module A is shown according to another embodiment of the present invention. Detailed Implementation

[0037] Figure 1 A non-limiting embodiment of a lab-on-a-chip (LOC) system 1 is illustrated schematically. The LOC system 1 of the illustrated embodiment is configured to perform preparation steps for biological samples and, for example, to perform CRISPR analysis on biological samples. However, the invention is not limited to this application and can also be used for various analyses, such as polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), proteomics analysis, and analysis of non-biological samples, or even other applications. During the analysis, biological or non-biological samples are eluted in an aqueous or oil-based liquid medium or fluid, or any other liquid solution.

[0038] The LOC system 1 includes a cartridge 2, which can be connected to a control device 3 (not part of this invention) via a first fluid connection 4 and an optional second fluid connection 4'. For example, the control device 3 is described in US2019 / 0201897. In one embodiment of the invention, the cartridge 2 is a disposable cartridge.

[0039] The control device 3 is designed to control the movement of fluids inside the cartridge 2 and to perform sample processing and analysis steps. For example, in one embodiment of the invention, the control device 3 performs the heating step required for CRISPR analysis of the biological sample inside the cartridge 2.

[0040] According to the present invention, the box 2 includes a fluid module A and a storage module B, which are fluidly connected to each other via a third fluid connection 6 and mechanically coupled to each other. The fluid module A can be connected to the control machine 3 via a first fluid connection 4.

[0041] The storage module B can be connected to the control machine 3 via a second fluid connection 4'. Alternatively, as described above, the second fluid connection 4' is absent, and the storage module B is connected to the external environment via a fluid connection (not shown) sealed by a waterproof membrane configured to allow air to flow through it.

[0042] In one embodiment, the first fluid connection 4 has a first portion 4a belonging to the fluid module A and a second portion 4b belonging to the control machine 3. The first portion 4a and the second portion 4b are designed to be coupled and sealed together. For example, the first portion 4a and the second portion 4b are respectively a male pneumatic connection and a female pneumatic connection (or respectively a female pneumatic connection and a male pneumatic connection). In another embodiment, the connection type of the first fluid connection 4 includes a needle configured to fit a rubber seat (e.g., 3D printed). Specifically, the needle is part of the control machine 3, and the rubber seat is part of the fluid module A, arranged in... Figure 2A Within the cavity 40.

[0043] The second fluid connection 4' is formed similarly to the first fluid connection 4, and includes corresponding features (in particular, the first part 4a' corresponding to part 4a and the second part 4b' corresponding to part 4b).

[0044] The third fluid connection 6 has a first part 6a belonging to fluid module A and a second part 6b belonging to storage module B. The first part 6a and the second part 6b are designed to be coupled and sealed together. For example, the first part 6a and the second part 6b are respectively a male Luer sleeve connection and a female Luer sleeve connection (or respectively a female Luer sleeve connection and a male Luer sleeve connection).

[0045] In one embodiment, the fluid module A includes a solid body 5, such as a generally parallelepiped or generally quadrilateral shape, the solid body 5 including a first portion 4a of a first fluid connection 4, a first portion 6a of a third fluid connection 6, a fluid circuit 8, a pneumatic circuit 10, and a storage chamber 12 configured to store (and in one embodiment, actually store) a desiccant, for example in the form of a bag containing silica beads or silica gel.

[0046] The fluid circuit 8 includes a fluid passage 14a, a fluid passage 14b, a first valve 15, a pyrolysis chamber 16, and one or more reaction chambers 18(1)-18(n). Fluid passage 14a connects the first portion 6a of the third fluid connection 6 to the pyrolysis chamber 16. Fluid passage 14b connects the pyrolysis chamber 16 to the reaction chambers 18(1)-18(n). Valve 15 is located in fluid passage 14b. The opening and closing of the first valve 15 can be controlled by the control machine 3 in a manner known per se. Valve 15 can be one of the following: a solenoid valve, a mechanical check valve, a resilient duckbill valve, a pneumatic valve, etc.

[0047] The pneumatic circuit 10 includes air paths 11a, 11b, 11c(1)-11c(n) and a second valve 17. Air path 11a connects the first portion 4a of the first fluid connection 4 to the storage chamber 12, air path 11b connects the storage chamber 12 to the pyrolysis chamber 16, and air paths 11c(1)-11c(n) connect the storage chamber 12 to the reaction chambers 18(1)-18(n), respectively. The second valve 17 is located in air path 11b. The opening and closing of the second valve 17 can be controlled by the control machine 3 in a manner known per se. Valve 17 can be one of the following: a solenoid valve, a mechanical check valve, a resilient duckbill valve, a pneumatic valve, etc.

[0048] The storage module B includes: a generally parallelepiped or essentially quadrilateral solid body 7 that houses a second portion 6b of the third fluid connection 6; a swab container or swab storage tube 22 configured to contain or store (and in one embodiment, actually store) liquid buffers and reagents, and adapted to contain a swab 24 having a head or tip suitable for biological sample collection; a fluid channel 26 configured to fluidly connect the swab container 22 to the second fluid connection 4' or the external environment according to the corresponding embodiments described above; a fluid channel 28; and, if present, a first portion 4a' of the second fluid connection 4'.

[0049] The swab container 22 is connected to the second part 6b of the third fluid connection 6 via the fluid channel 28.

[0050] Figure 2A The top view of the xz plane shows fluid module A in a three-axis system where the axes x, y, and z are orthogonal to each other. Figure 2B The fluid module A in the exploded diagram is shown schematically in a triaxial system with axes x, y, and z that are orthogonal to each other.

[0051] The main body 5 of fluid module A is formed by three parts (such as...) Figure 2B (As shown in the exploded view), it includes a first part 50, a second part 51, and a third part 52. The first part 50 has a front surface 50a and a back surface 50b that are opposite each other along the y-axis, a top surface 50c and a bottom surface 50d that are opposite each other along the z-axis, and a first side surface 50e and a second side surface 50f that are opposite each other along the x-axis. The front surface 50a is connected to the back surface 50b through the top surface 50c, the bottom surface 50d, the first side surface 50e, and the second side surface 50f.

[0052] The second part 51 has a front surface 51a and a back surface 51b that are opposite each other along axis y, a top surface 51c and a bottom surface 51d that are opposite each other along axis z, and a first side surface 51e and a second side surface 51f that are opposite each other along axis x. The front surface 51a is connected to the back surface 51b through the top surface 51c, the bottom surface 51d, the first side surface 51e, and the second side surface 51f.

[0053] The third part 52 has a front surface 52a and a back surface 52b that are opposite each other along axis y, a top surface 52c and a bottom surface 52d that are opposite each other along axis z, and a first side surface 52e and a second side surface 52f that are opposite each other along axis x. The front surface 52a is connected to the back surface 52b through the top surface 52c, the bottom surface 52d, the first side surface 52e, and the second side surface 52f.

[0054] The second part 51 is bonded to the first part 50 at the front 50a of the first part 50; and the third part 52 is bonded to the first part 50 at the back 50b of the first part 50.

[0055] When parts 50 and 52 are glued together, the back side 51b of the second part 51 faces the front side 50a of the first part 50, and the front side 52a of the third part 52 faces the back side 50b of the first part 50. The front side 51a of the second part 51 forms the front side 5a of the main body 5; the back side 52b of the third part 52 forms the back side 5b of the main body 5; the top surfaces 51c, 50c, and 52c together form the top surface 5c of the main body 5; the bottom surfaces 51d, 50d, and 52d together form the bottom surface 5d of the main body 5; the first side surfaces 51e, 50e, and 52e and the second side surfaces 51f, 50f, and 52f together form the first side surface 5e and the second side surface 5f of the main body 5.

[0056] Parts 50-52 are bonded together, for example by adhesive or thermal welding, and may have gaskets and sealing components (not shown) to prevent liquid leakage and to ensure that the individual channels are separated from each other and isolated from the external environment. In one embodiment, the second part 51 is a transparent strip or film. The first part 50 and the third part 52 are made of, for example, plastic or polymer materials, or of biocompatible materials suitable for performing the above-described bioanalyses.

[0057] During use, when the box 2 is connected to the control machine 3, the bottom surface 5d of the main body 5 faces the control machine 3 and the top surface 5c faces away from the control machine 3.

[0058] The third part 52 includes a cavity 40 at the bottom surface 52d and the front surface 52a, the cavity 40 having a main extension along the second axis z toward the top surface 52c.

[0059] The first portion 50 includes a first through-hole 110a that extends parallel to a first direction y from the back side 50b through the first portion 50 to the front side 50a. The first portion 50 also includes a second through-hole 113a that extends parallel to the first direction y from the back side 50b through the first portion 50 to the front side 50a. The first through-hole 110a and the second through-hole 113a are spaced apart from each other by a certain distance, specifically along the axis z.

[0060] When the third part 52 is bonded to the first part 50, the cavity 40 forms a hole 40a in the bottom surface 5c of the solid body 5 at one end, and the cavity 40 faces the through hole 110a at the opposite end.

[0061] Aperture 40a and cavity 40 are at least partially formed Figure 1 The first part 4a of the first fluid connection 4.

[0062] The first part 50 also includes a first air recess 112a at the front 50a, the first air recess 112a being located near the side 5f and having a main extension along the axis z.

[0063] The first through hole 110a connects the cavity 40 to the first air groove 112a.

[0064] When the second part 51 is bonded to the first part 50, the first air groove 112a forms part of the first air path 11a. The first air groove 112a extends from the through hole 110a parallel to the axis z toward the top surface 50c until the second through hole 113a. The aperture 40a, cavity 40, first through hole 110a, first air groove 112a, and second through hole 113a are located in the portion of the main body 5 near the side 5f.

[0065] The third portion 52 includes a second air recess 114a at the front surface 52a. When portion 50 is bonded to portion 52, a second through-hole 113a connects the first air recess 112a to the second air recess 114a. When the third portion 52 is bonded to the first portion 50, the second air recess 114a forms another portion of the first air path 11a. The second air recess 114a extends parallel to axis x toward the side surface 50e, reaching a third through-hole 115a that extends through the first portion 50 within the storage chamber 12. Thus, the interior of the storage chamber 12 is in air connection with the aperture 40a, especially when the second portion 51 is coupled to the first portion 50 and protects the interior of the storage chamber 12 from the external environment.

[0066] A portion of the second air path 11b is formed by a third air groove 110b, which extends parallel to axis x at the front surface 50a. The third air groove 110b exits the storage chamber 12 on the opposite side of the storage chamber 12 relative to the second air groove 114a.

[0067] The third portion 52 includes a fourth air recess 112b at the front 52a, which extends primarily along the x-axis toward the side 52e. The third air recess 110b is connected to the fourth air recess 112b by a through-hole 111b formed through the first portion 50.

[0068] The first part 50 includes a valve hole 17a, which is a through hole connecting the back side 50b to the front side 50a.

[0069] The fourth air groove 112b terminates at the corresponding portion of the valve hole 17a in the first part 50. The valve hole 17a accommodates the valve 17.

[0070] Part 50 also includes a lysis chamber 16, where a lysis step is performed during use to extract nucleic acids from cells present in a biological sample.

[0071] The first portion 50 also includes a groove 114b at the front surface 50a, which forms another portion of the second air path 11b, which extends primarily along axis z toward the bottom surface 50d and connects the valve port 17a to the pyrolysis chamber 16. A fluid inlet port 14a' connects the upper portion of the pyrolysis chamber 16 to a fluid passage 14a. The fluid passage 14a extends parallel to axis x from the fluid inlet port 14a' toward the first side surface 5e of the body 5 at the front surface 52a of the third portion 52, terminating at the first portion 6a of the fluid connection 6. The first portion 6a includes a through-hole 60a in fluid communication with the fluid passage 14a. Specifically, in Figure 2A In the embodiment shown, the first part 6a is a male Luer sliding connector.

[0072] The first part 50 also includes fluid recesses 140a and 140c, valve port 15a, through port 141, and multiple (three in this case) reaction chambers 18(1), 18(2), and 18(3). The first part 50 includes fluid recess 140b.

[0073] Fluid groove 140a extends from the lower portion of the pyrolysis chamber 16 (opposite to the upper portion along the z-axis) at the front 50a and extends mainly parallel to the z-axis toward the top surface 50c of the first portion 50, terminating at valve orifice 15a. Valve orifice 15a is a through-hole connecting the front 50a and the back 50b and accommodating valve 15. Fluid groove 140b extends from the front 52a of the third portion 52, with its main extension substantially parallel to the x-axis. When portions 50 and 52 are bonded together, fluid groove 140b faces valve orifice 15a at one end and through-hole 141 at the opposite end. Fluid groove 140c extends from the front 50a of the third portion 50 toward the bottom surface 50d of the first portion 50 from through-hole 141, where it forms three branches 140c', 140c”, and 140c”’, each branch reaching a corresponding reaction chamber 18(1), 18(2), and 18(3).

[0074] The fluid groove 140a, valve hole 15a, fluid groove 40b, through hole 141, and fluid groove 140c are formed as a single unit. Figure 1 Fluid channel 14b.

[0075] When portions 50 and 52 are bonded together, the lysis chamber 16 and reaction chambers 18(1), 18(2), and 18(3) are sealed on one side by the second portion 51 and on the opposite side by the third portion 52. In one embodiment, the third portion 52 houses two heaters 9 and 13 (of a known type). When the first portion 50 and the third portion 52 are bonded together, one heater 9 is arranged corresponding to the lysis chamber 16, and the other heater 13 is arranged corresponding to the reaction chambers 18(1), 18(2), and 18(3). The heater 9 may be controlled by the control machine 3 to perform a heating step of the lysis chamber, for example, heating at 95°C for 5 minutes to extract nucleic acids from cells present in a biological sample during an exemplary CRISPR analysis. The heater 13 may be controlled by the control machine 3 to maintain reaction chambers 18(1)-18(3) at a fixed temperature, for example, 37°C.

[0076] Depending on the specific analysis to be performed, the temperature achieved by heaters 9 and 13 may differ from the example above.

[0077] The first part 50 also includes a plurality of (three here) fluid grooves 110c(1), 110c(2), 110c(3), a plurality of (six here) through-holes 111c(1)-111c(6), and a plurality of (three here) air grooves 112c(1), 112c(2), and 112c(3). The third part 52 also includes a groove 80, such as a rectangular groove, which accommodates a membrane 81 that is permeable to gases and vapors but impermeable to liquids. The membrane 81 is, for example, a layer of material that is impermeable to liquids (waterproof fabric) but permeable to air and vapors (breathable fabric), such as a PTFE membrane.

[0078] Alternatively to membrane 81, an equivalent permeable membrane can be used (e.g., a membrane with pores or a permeable PDMS layer).

[0079] Fluid grooves 110c(1), 110c(2), and 110c(3) extend from the front surface 50a of the first part 50, with the main extensions being substantially parallel to the z-axis. Fluid grooves 110c(1), 110c(2), and 110c(3) exit from the corresponding upper portions of reaction chambers 18(1), 18(2), and 18(3) and reach through holes 111c(1), 111c(2), and 111c(3), respectively. Through holes 111c(1), 111c(2), and 111c(3) connect the front surface 50a of the first part 50 to the back surface 50b. Vias 111c(4), 111c(5), and 111c(6) are spaced a certain distance from vias 111c(1), 111c(2), and 111c(3) along axis z, such that vias 111c(4), 111c(5), and 111c(6) are closer to the top surface 50c of the first part 50 than 111c(1), 111c(2), and 111c(3). In addition, vias 111c(4), 111c(5), and 111c(6) are substantially aligned with vias 111c(1), 111c(2), and 111c(3) along axis z.

[0080] Air grooves 112c(1), 112c(2), and 112c(3) extend from the front surface 50a of the first part 50, with the main extensions being substantially parallel to the axis z. They respectively connect the via 111c(4) to the storage chamber 12, the via 111c(5) to the storage chamber 12, and the via 111c(6) to the storage chamber 12. When the first part 50 and the third part 52 are bonded together, the groove 80 faces the via 111c(1)-111c(6) in such a way that the membrane 81 fluidly connects the vias 111c(1)-111c(3) to the vias 111c(4)-111c(5).

[0081] The fluid grooves 110c(1)-110c(3), the vias 111c(1)-111c(3), the membrane 81 in the groove 80, the vias 111c(4)-111c(6), and the air grooves 112c(1)-112c(3) are formed as a whole. Figure 1 The air path 11c(1)-11c(n) connects the reaction chamber 18(1)-18(8) to the storage chamber 12.

[0082] Reaction chambers 18(1)-18(n) are configured to store (and in one embodiment, they store) lyophilized reagents or freeze-dried reagents prior to their use for analysis of samples. In a non-limiting example described herein, reaction chambers 18(1)-18(n) are configured to store (and in one embodiment, they store) lyophilized enzymes required for a step of performing CRISPR analysis. In another non-limiting example (not described), reaction chambers 18(1)-18(n) are configured to store (and in one embodiment, they store) lyophilized antibodies and enzymes required for a step of performing ELISA analysis in a manner known per se. In another non-limiting example (not described), reaction chambers 18(1)-18(n) are configured to store (and in one embodiment, they store) lyophilized antibodies immobilized on magnetic beads required for a step of performing protein biosensing in a manner known per se. In another non-limiting example (not described), reaction chambers 18(1)-18(n) are configured to store (and in one embodiment, they store) lyophilized reagents required for steps of performing PCR analysis in a manner known per se. Clearly, other applications are also possible, wherein reaction chambers 18(1)-18(n) can be configured to store (and in one embodiment, actually store) specific lyophilized reagents, or dry reagents, or desiccated reagents, or solid reagents, for use in steps of analysis performed by System 1 during use.

[0083] During the shelf life of fluid module A in box 2, when storage chamber 12 stores desiccant and reaction chambers 18(1)-18(n) store dry reagents, or lyophilized reagents, or solid reagents (hereinafter referred to as "dry reagents"), the desiccant prevents the hydration of the reagents. This prevention of hydration improves the lifespan of the dry reagents compared to when the desiccant is placed in an outer package (which in turn contains fluid module A), thus improving the overall lifespan of fluid module A. In fact, the presence of desiccant in storage chamber 12 allows for the capture of water vapor that may (even accidentally) reach fluid module A from the external environment before packaging or during its shelf life.

[0084] During the use of box 2, the desiccant in storage chamber 12 also protects the dry reagent from hydration during the bioanalytical steps, when liquid flows in fluid module A, but the reagent still needs to be kept dry.

[0085] Figure 3A Schematic illustration of the work by Figure 1 and Figure 2A The air and liquid inside the fluid module A shown follow the paths described above, for example, during the CRISPR analysis of a biological sample. During the analysis phase shown, fluid module A is connected to storage module B (not shown) via fluid connection 6, and fluid module A is connected to control machine 3 (not shown) via fluid connection 4.

[0086] exist Figure 3A During this phase, control unit 3 opens valve 17 and closes valve 15. Additionally, control unit 3 draws air from fluid module A via fluid connection 4, generating an airflow 30 along air path 11a. Airflow 30 draws air back from storage chamber 12, creating a negative pressure within storage chamber 12. The negative pressure in storage chamber 12 draws air back from lysis chamber 16 along air path 11b and the open valve 17, generating an airflow 32. Airflow 32 generates a negative pressure in lysis chamber 16. The negative pressure in lysis chamber 16 draws liquid back from storage module B (in the illustrated example, this is the biological sample to be analyzed, with added liquid buffer and reagents) via fluid connection 6 and fluid channel 14a, generating a liquid flow 34. Liquid flow 30 at least partially fills lysis chamber 16.

[0087] In the embodiment described, the control machine 3 then controls the heater 9 to perform a heating step. During the heating step, the liquid in the lysis chamber 16 is heated to a high temperature, for example, in the range of 90 to 99°C, such as 95°C, and is maintained at said temperature for, for example, 3 to 10 minutes, such as 5 minutes, to extract nucleic acids from cells present in the biological sample. During the heating step, a portion of the liquid evaporates. The evaporated liquid leaves the lysis chamber 16 as vapor through air path 11b. The vapor is at least partially captured by the desiccant in the storage chamber 12, and optionally, the vapor is at least partially extracted by the control machine 3 through air path 11a, thus preventing premature hydration of the dry reagent stored in reaction chambers 18(1)-18(n).

[0088] Figure 3B The subsequent stages of the analysis are shown. In Figure 3BDuring this phase, control machine 3 closes valve 17 and opens valve 15. Additionally, control machine 3 draws air from fluid module A via fluid connection 4, generating airflow 30 via air path 11a. Airflow 30 draws air back from storage chamber 12, generating negative pressure within storage chamber 12. The negative pressure in storage chamber 12 draws air back from reaction chambers 18(1)-18(3) along air paths 11c(1)-11c(3), generating airflows 36(1)-36(3) respectively in air paths 11c(1)-11c(3). Airflows 36(1)-36(3) generate negative pressure in reaction chambers 18(1)-18(3). The negative pressure in reaction chambers 18(1)-18(3) draws liquid back from pyrolysis chamber 16 via fluid path 14b and the opened valve 15, generating liquid flow 38. The liquid stream 38 is split into three streams 38', 38”, and 38”', which respectively reach and at least partially fill reaction chambers 18(1)-18(3), and hydrate the dry reagent stored in the reaction chambers. In this embodiment, the control machine 3 then controls the heater 13 to maintain a constant temperature (e.g., 37°C) in the reaction chambers 18(1)-18(3) to perform the CRISPR analysis steps in a manner known per se. During this stage, the liquid is able to completely fill the reaction chambers 18(1)-18(3) and partially fill the air paths 11c(1)-11c(3) up to the membrane 81. The membrane 81 (which is waterproof as described above) prevents the liquid from reaching the storage chamber 12, thereby emptying the reaction chambers 18(1)-18(3). In this way, the membrane 81 also prevents contact between the liquid and the desiccant stored in the storage chamber 12, thus avoiding undesirable absorption and any possible contamination (or degradation) of the sample to be analyzed due to contact between the sample and the desiccant. It should be noted that during this stage, valve 17 remains closed to prevent liquid from flowing into storage chamber 12 along air path 11b.

[0089] Figure 4A A portion of one embodiment of the storage module B of box 2 is shown, including swab container 22.

[0090] In one embodiment, the swab container 22 is made of a biocompatible plastic material. In a non-limiting example, the swab container 22 is made of polypropylene and manufactured using techniques known in the art for manufacturing medical packaging.

[0091] The swab container 22 has a substantially hollow cylindrical shape, terminating at one end with a generally circular bottom wall 22a, at the opposite end with a generally circular opening 22b, and a solid side wall 22c connecting the bottom wall 22a and the opening 22b. The side wall 22c includes an inner surface 220 facing the interior of the hollow cylinder and an outer surface 222 facing the exterior of the cylinder, opposite the inner surface 220.

[0092] In the illustrated embodiment, the sidewall 22c includes a portion 224 near the opening 22b, which includes external threads 223 on the outer surface 222.

[0093] In another embodiment (not shown), the internal thread exists on the inner surface 220 of portion 224, rather than the external thread 223 on the outer surface 222.

[0094] The portion 226 of the swab container 22 near the bottom wall 22a accommodates a plurality of protrusions or fins 225(1)-225(5) on its inner surface 220. The fins 225(1)-225(5) project radially inward from the inner surface 220 toward the main axis of the cylinder. In one embodiment, the fins 225(1)-225(5) extend longitudinally along the cylinder. In one embodiment, the fins 225(1)-225(5) reach the bottom wall 22a; in another embodiment, the fins 225(1)-225(5) are spaced a distance from the bottom wall 22a.

[0095] The swab container 22 also includes a protrusion 227 that extends outward from a sub-portion of portion 226 at the outer surface 222, specifically near the bottom wall 22a. The protrusion 227 terminates at surface 227a, such as a flat surface. A through-hole 228 extends from surface 227a toward the interior of the cylinder, connecting surface 227a to the inner surface 220.

[0096] In one embodiment, the protrusion 227 and the through-hole 228 together form the second portion 6b of the fluid connection 6. Specifically, the protrusion 227 and the through-hole 228 form a female Luer slide connector.

[0097] Before use, the through-hole 228 can be sealed by the rupture membrane 229. The rupture membrane 229 is configured to rupture when the reservoir module B is coupled to the fluid module A, thereby fluidly connecting the interior of the swab container 22 to the fluid channel 14a.

[0098] The portion 221 of the swab container 22, which is included between portions 226 and 224, is more flexible and elastic than portions 224 and 226 (e.g., by making it thinner), such that only portion 221 bends or deforms inward under the negative pressure generated by the control machine 3 to draw liquid back from module B (generating the aforementioned liquid flow 34). The degree of deformation of portion 221 can be adjusted by regulating the pressure generated by the control machine 3, and even the direction of flow 34 (and flow 38) can be reversed as needed.

[0099] For example, the thicker portions 224 and 226 have a thickness ranging from 1 to 1.5 mm, and the thinner portion 221 has a thickness ranging from 0.4 to 1 mm, particularly 0.5 to 0.6 mm.

[0100] Figure 4B A swab container 22 containing a swab 24 is shown. In the illustrated embodiment, the swab 24 is coupled to or integral with an internally threaded cap 240. The internally threaded cap 240 may be coupled to a thread 223. When the swab 24 is inserted into the swab container 22 and the internally threaded cap 240 is screwed onto the external thread 223, the interior of the swab container 22 is effectively isolated from the external environment, and the tip of the swab is compressed by fins 225(1)-225(5), releasing the biological material previously collected by the tip. The biological material released by the compression action is eluted into a liquid buffer or liquid medium contained within the swab container 22. The liquid buffer or medium may be manually inserted into the swab container, or it may be pre-stored in the swab container during its manufacture.

[0101] In another embodiment (not shown), the swab 24 is coupled to or integrated with the external threaded cap when the internal thread exists on the inner surface 220 of the swab container instead of the external thread 223 on the outer surface 222 of the swab container.

[0102] Figure 5A and Figure 5B Different embodiments of the invention are shown. Figure 5A and Figure 5B In the fluid module A and / or storage module B, the components related to... Figures 1 to 4A and Figure 4B The common elements of fluid module A and / or storage module B are indicated by the same reference numerals and are not described again.

[0103] exist Figure 5A and Figure 5B In the illustrated embodiment, the fluid module A further includes an integral swab container 22'; the fluid module A and the swab container 22' are either integral or separate pieces.

[0104] refer to Figure 2A And as Figure 5A As shown, the swab container 22' extends as a continuation of the side 5e. To accommodate the swab container 22' within the side 5e and ensure proper fluid connection with the fluid circuit 8, in Figure 5A In this embodiment, a first portion 6a of the fluid connection 6 is formed on the side of the swab container 22' and fluidly coupled to the swab container, as better described below. That is, the swab container 22' extends between the first portion 6a of the fluid connection 6 and the through-hole 14a'. In this embodiment, the side 5e of the body 5 is the side of the swab container 22'.

[0105] The swab container 22' includes a groove 200, an aperture 206 located at one end of the groove 200 for inserting a swab, and a through hole 202 that forms an inlet for a buffer solution during use.

[0106] The groove 200 extends at the front surface 50a of the first portion 50, and its main dimensions are substantially parallel to the axis z between the top surface 50c (where the aperture 206 is present) and the bottom surface 50d of the first portion 50 (not reaching the bottom surface 50d). When the first portion 50 and the second portion 51 are bonded together, the groove 200 forms a swab container 22'.

[0107] The via 202 connects the front side 50a of the first part 50 to the back side 50b of the first part 50.

[0108] The first portion 6a of the fluid connection 6 is formed on a physical support protruding from the side 5e of the swab container 22'. The through-hole 202 is fluidly connected to the first portion 6a.

[0109] The swab container 22' is fluidly connected to the lysis chamber 16 via the fluid channel 14a.

[0110] In one embodiment, a plastic cap 208 is attached to the body 5 via a flexible mechanical connection 207, and the plastic cap 208 is adapted to seal the aperture 206 when the swab is contained in the swab container 22'. In another embodiment (not shown), the cap adapted to seal the aperture 206 is integral with the swab at one end of the stick or rod of the swab. In yet another embodiment, the cap adapted to seal the aperture 206 is detachable from the body 5 and the swab stick.

[0111] In one embodiment, the fluid module A further includes one or more protruding mechanical connectors (hereinafter also referred to as "pins") 210 and one or more protruding guides 212, for example, in the form of an inclined plane relative to the surface of the front face 5a of the body 5. A pin 210 in... Figure 5A and Figure 5B It is shown in the middle.

[0112] Pin 210 includes a body 210a and a head 210b, and is, for example, mushroom-shaped or T-shaped. The body 210a of pin 210 extends from a first side 5e of the swab container 22', away from the first side 5e, with its main dimension parallel to axis x. The head 210b extends at one end of the body 210a, opposite the other end of the body 210a that is physically coupled to side 5e. In one example, the main dimension of the head 210b is perpendicular to the main dimension of the body 210a, such that the head 210b protrudes laterally from or projects laterally from the body 210a. The lateral protrusion of the head 210b forms an interlocking mechanism, which, as explained better later, is used when the storage module B is coupled to... Figure 5A In the embodiment, fluid module A keeps storage module B in a fixed position.

[0113] The protruding guide 212 also extends at the first side 5e of the main body 5, at a certain distance from the pin 210. The protruding guide 212 has the function of coupling the storage module B to... Figure 5A In the embodiment, fluid module A facilitates the alignment of storage module B. The protruding guide 212 also acts as a blocking component to prevent separation of storage module B from fluid module A (and vice versa).

[0114] The physical body 7 of the storage module B has a front side 7a and a back side 7b that are opposite each other along axis y, a top side 7c and a bottom side 7d that are opposite each other along axis z, and a first side side 7e and a second side side 7f that are opposite each other along axis x. The front side 7a is physically connected to the back side 7b through the top side 7c, the bottom side 7d, the first side side 7e, and the second side side 7f.

[0115] The body 7 includes one or more openings, slits, or sockets 710 adapted to physically couple with one or more pins 210 of the fluid module A. For example, the opening 710 is formed as a groove located at the front face 7a and extends from the first side face 7e to the second side face 7f. The opening 710 has dimensions that match the body 210a, allowing the body 210a to be inserted into the opening 710, and the protrusion of the head 210b contacts the first side face 7e.

[0116] The main body 210a can act as a pivot point to facilitate the alignment and coupling of the storage module B and the fluid module A.

[0117] The main body 7 also includes one or more protruding guides 712 (e.g., one or more inclined planes) on the second side 7f, the one or more protruding guides 712 being configured to couple with the corresponding side of the fluid module A to couple with the protruding guide 212.

[0118] According to the above embodiment, when fluid module A and storage module B are coupled together, pin 210 engages in the sleeve formed by opening 710, thereby establishing a mechanical connection between fluid module A and storage module B (see [link]). Figure 5B Additionally, when fluid module A and storage module B are coupled together, protruding guide 712 is pressed against protruding guide 212 until protruding guide 712 is engaged below protruding guide 212 by bending protruding guide 212. In other words, guides 212 and 712 operate as a snap-fit ​​mechanism.

[0119] The mechanical connection provided by pin 210 when it is engaged in the opening and by protruding guides 212, 712 allows for precise alignment and avoids unwanted relative movement between the two modules A and B.

[0120] In another embodiment (not shown), one or more pins 210 are on the storage module B, and one or more openings 710 are on the fluid module A.

[0121] exist Figure 5A In one embodiment, the physical body 7 of the storage module B includes: an air inlet 714 (which at least partially forms the first portion 4a' of the previously described second connection 4'), a storage chamber 716, a via 718, a via 720, an air passage 722, a via 724, a via 726, and a fluid passage 728.

[0122] Air inlet 714 is formed by a cavity extending from the bottom side 7d of the body. A through-hole 718 connects air inlet 714 to air passage 722. Air passage 722 extends from the front side 7a of the body 7, connecting through-hole 718 to air passage 720. Through-hole 720 connects air passage 722 to reservoir chamber 716. Through-hole 720 is located in an area of ​​reservoir chamber 716 that cannot be reached by the liquid solution / buffer contained within the reservoir during use.

[0123] The storage chamber 716 extends at the rear side 7b of the main body 7. The storage chamber 716 is sealed, for example, by a film or by adhesive or glue to the plastic wall of the rear side 7b of the main body 7.

[0124] Via 724 connects the reservoir chamber 716 to the fluid channel 728. The fluid channel 728 extends at the front 7a of the body 7, connecting via 724 to via 726. A second via 726 connects the fluid channel 728 to the second portion 6b of the fluid connection 6.

[0125] Through-holes 718, air passages 722, 720, 724, fluid passages 728, and 726 are sealed, for example, by transparent strips or films, or by adhesive or glue to the plastic wall on the front side 7a of the body 7, protecting them from external environmental influences and preventing liquid leakage.

[0126] When fluid module A and reservoir module B are coupled together, alignment provided by pin 210 with opening 710 and by protruding guides 212 and 712 further ensures proper coupling between the first portion 6a and the second portion 6b of fluid connection 6. A ruptureable membrane or removable cap can be used to seal the second portion 6b to prevent liquid leakage before use. The ruptureable membrane can be configured to rupture when the second portion 6b is coupled to the first portion 6a.

[0127] Figure 6 Further embodiments of the invention are shown. Figure 6 In the middle, storage module B and Figure 5A The same as that already described and shown. However, with Figure 5A The difference is that, in Figure 6 In this configuration, the lysis chamber 16 extends to the top surface 5c of the body 5 and is configured (shaped) to accommodate the swab 24. In other words, the swab container 22' and the lysis chamber 16 are formed by a common recess that is fluidly connected to the reaction chambers 18(1)-18(n) via fluid channels 14b.

[0128] According to another embodiment of the present invention, such as Figure 7 As shown, the main body 5 of fluid module A is formed by three parts (as shown in the figure). Figure 7 (As shown in the exploded view), it includes a first part 50, a second part 51, and a third part 52. Unlike the previously described embodiments, in... Figure 7 In some embodiments, the second portion 51 and the third portion 52 include corresponding strips or films. Specifically, the third portion 52 may be formed of multiple components, including film or strip portions 52' and one or more portions 52' of semiconductor material (e.g., silicon), which are glued and / or mechanically inserted into the first portion 50.

[0129] In this embodiment, the elements previously described as part of the third part 52 are instead formed on the back surface 50b of the first part 50. The front surface 50a of the first part 50 is as described above. The elements formed on the back surface 50b of the first part 50 specifically include a second air recess 114a, a fourth air recess 112b, a fluid channel 14a, a fluid recess 140b, and a recess 80 (accommodating membrane 81). Furthermore, the cavity 40 extends at the bottom surface 50d of the first part 50.

[0130] As part of the third part 52, one or more semiconductor material portions 52” form heaters 9, 13.

[0131] It should be noted that in all disclosed embodiments, both the fluid module A and the storage module B of cartridge 2 are suitable for storing dry reagents (in module A) and liquid buffers / reagents (in module B) before use. More specifically, fluid module A is configured to store dry reagents in a humidity-controlled environment, such as by a desiccant in storage chamber 12; storage module B is configured to store liquids in storage chamber 716 or swab container 22 (according to a corresponding embodiment). Fluid module A may be coupled to storage module B. Since fluid module A is a separate physical entity relative to storage module B, the present invention allows the two modules A and B to be manufactured according to corresponding separate processes, even in different manufacturing environments or plants. For example, the manufacture and packaging of fluid module A can be performed in a controlled environment with low relative humidity, thereby reducing potential sources of contamination or undesirable hydration of the dry reagent. The manufacture and packaging of storage module B can instead be performed in an environment with more relaxed restrictions, thus limiting production costs. Furthermore, different technologies can be utilized for the manufacture of fluid module A, relative to the manufacture of storage module B.

Claims

1. A box for lab-on-a-chip applications, comprising: The first module includes: At least one desiccant storage compartment; Dry reagent storage room; A fluid circuit, which is fluidly connected to the dry reagent storage chamber; A first air path connects the dry reagent storage chamber to the at least one desiccant storage chamber, and the first air path includes a membrane that is impermeable to liquids but permeable to gases and vapors, the membrane being arranged in the first air path in a manner that prevents liquid flow from the dry reagent storage chamber to the at least one desiccant storage chamber. The second module includes a container having an internal cavity for containing a liquid solution. The first module and the second module each have a corresponding first fluid connector and a second fluid connector, which are adapted to be fluidly coupled to each other; and The first fluid connector of the first module is fluidly coupled to the fluid circuit, and the second fluid connector of the second module is fluidly coupled to the container.

2. The cassette for lab-on-a-chip applications according to claim 1, further comprising one or more desiccants and one or more drying reagents, the one or more desiccants being in the at least one desiccant storage compartment and the one or more drying reagents being in the drying reagent storage compartment.

3. The box for lab-on-a-chip applications according to claim 1, wherein the first module comprises a first layer and a second layer, the first layer and the second layer being coupled to each other; The first air path includes: The first part, which is in the first layer, is fluidly connected to the dry reagent storage chamber; The second part, which is located in the second layer; The third part, which is in the first layer, is fluidly connected to the at least one desiccant storage chamber; A first through-hole, extending through the first layer, fluidly connected to the first portion of the first air path, and coupled via the membrane to the second portion of the first air path by air; and A second through-hole extends through the first layer, is fluidly connected to the third portion of the first air path, and is coupled to the second portion of the first air path via air through the membrane.

4. The box for lab-on-a-chip applications according to claim 1, wherein the first module includes a first layer having a first surface and a second surface, the first surface and the second surface being opposite to each other; The first air path includes: The first part, located on the first surface of the first layer, is fluidly connected to the dry reagent storage chamber; The second part is located on the second surface of the first layer; The third part, located on the first surface of the first layer, is fluidly connected to the at least one desiccant storage chamber; A first through-hole, extending from the first surface through the first layer to the second surface, is fluidly connected to the first portion of the first air path and coupled via the membrane to the second portion of the first air path; and The second through-hole extends from the first surface through the first layer to the second surface, is fluidly connected to the third portion of the first air path, and is coupled to the second portion of the first air path via air through the membrane.

5. The box for lab-on-a-chip applications according to claim 4, wherein the first module comprises a second layer and a third layer; The second layer includes a strip or film coupled to the first surface of the first layer, the strip or film being configured to seal the fluid circuit, the at least one desiccant storage chamber, and the dry reagent storage chamber; and The third layer includes at least one strip or at least one thin film, and at least one heating element of semiconductor material, wherein the at least one strip or the at least one thin film is coupled to the second surface of the first layer, and the at least one heating element is coupled to the second surface of the first layer.

6. The box for lab-on-a-chip applications according to claim 1, wherein the first module and the second module have corresponding mechanical coupling components for mechanically coupling the first module to the second module.

7. The cassette for lab-on-a-chip applications according to claim 1, wherein the first fluid connector and the second fluid connector are Luer connectors.

8. The cassette for lab-on-a-chip applications according to claim 1, wherein the container is a sample collection container comprising a swab having a tip, a rod, and a cap, the rod being coupled to the tip and the cap being coupled to the rod; The container has a threaded opening for inserting the swab into the internal cavity; The cap of the swab is a threaded cap, adapted to seal the internal cavity when the swab is inserted into the container and the threaded cap is screwed onto the threaded opening; and The container includes a first portion of deformable material configured to undergo elastic deformation when internal pressure is applied.

9. The cassette for lab-on-a-chip applications according to claim 8, wherein the container includes a second portion having a protrusion within the internal cavity such that when the swab is inserted into the container, the tip contacts the protrusion; and The second part is configured to withstand the internal pressure without deformation.

10. The cassette for lab-on-a-chip applications according to claim 9, wherein the second fluid connector includes a via through which the via passes through the container at the second portion, the elastic deformation being caused during use by pumping the liquid solution out of the container.

11. The cassette for lab-on-a-chip applications of claim 1, further comprising a second air path that connects the at least one desiccant storage chamber to an outlet opening of the cassette via air, the outlet opening being configured for connection to an external control unit for air suction.

12. The cassette for lab-on-a-chip applications of claim 1, further comprising a sealing layer coupled to the first module to seal the fluid circuit, the at least one desiccant storage chamber, and the dry reagent storage chamber.

13. The cassette for lab-on-a-chip applications according to claim 1, wherein the fluid circuit comprises: Reaction chamber; A first fluid channel fluidly connects the first fluid connector to the reaction chamber; as well as A second fluid channel fluidly connects the reaction chamber to the dry reagent storage chamber.

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