WO2024231149A1

WO2024231149A1 - Fluidic cartridge with an analyte detection member

Info

Publication number: WO2024231149A1
Application number: PCT/EP2024/061733
Authority: WO
Inventors: Robert E. Schneider; Ben SETTERQUIST; Mackenzie AMIDEI; Scott Schmidt; Mark Mayernick; James Hutchison; Tom Vincent; Laurin DIENER; Anna Katharina ELMER; Marion GILSDORF; Serej D. LEY; Melanie SCHÄPERS; Jacob BÖROLD
Original assignee: Sefunda Ag
Current assignee: Sefunda Ag
Priority date: 2023-05-11
Filing date: 2024-04-29
Publication date: 2024-11-14
Anticipated expiration: 2025-11-11

Abstract

A fluidic cartridge (10) is provided, comprising: an analyte detection member (42) including a fluid inlet section (40) and an analyte detection section (36) fluidly connected to the fluid inlet section (40), wherein the analyte detection section (36) includes a detection chamber (38) and a venting chamber (50) fluidly connected to the detection chamber (38), wherein the venting chamber (50) is at least partially closed by a semipermeable membrane (64) that is permeable for air and non-permeable for liquid. The fluidic cartridge (10) further comprises a foil (62) configured for covering the detection chamber (38), wherein the foil (62) is transparent or translucent and configured for permitting illumination of the detection chamber (38) and/or detection of visible and/or ultraviolet light therethrough, and wherein the foil (62) and the semipermeable membrane (64) are arranged on opposite sides of the analyte detection member (42).

Description

Fluidic Cartridge with an Analyte Detection Member

The present invention relates to a fluidic cartridge. In particular, the present invention relates to a fluidic cartridge which can be used for testing and/or analyzing samples such as biological samples.

Sample testing and analyzing is a discipline that has developed rapidly during the last years and decades. It originated from basic biochemistry and molecular biology research procedures, but since then has evolved into a discipline focused on routine analysis and high-throughput testing.

One of many approaches which have helped in this transformation is the use of fluidic cartridges. Fluidic cartridges are self-contained components which - in combination with other modules and/or units - facilitate the testing and analysis of samples (such as blood, urine, saliva and other samples). Usually, the sample is put onto the fluidic cartridge. The sample is then moved within the cartridge through various sites of the cartridge to perform different actions on the sample, such as cleaning/washing of the sample, extraction of deoxyribonucleic or ribonucleic acid (DNA, RNA) and/or performing a polymerase chain reaction (PCR).

For some of these actions, analytes need to be tested and/or detected. Therefore, fluidic cartridges usually include one or more detection wells (also referred to as detection chambers). The analytes to be tested and/or detected are introduced into these wells or chambers. It has been found, however, that testing and/or detection of analytes may be inaccurate or erroneous. Thus, there is a need for a fluidic cartridge which provides for a more accurate testing and/or detection of analytes.

This task is solved by the subject-matter of the independent claim. Further embodiments and developments are provided in the dependent claims.

According to an aspect of the present invention, a fluidic cartridge is provided. The fluidic cartridge comprises an analyte detection member. The analyte detection member includes a fluid inlet section and an analyte detection section fluidly connected to the fluid inlet section. The analyte detection section includes a detection chamber and a venting chamber fluidly connected to the detection chamber. The venting chamber is at least partially closed by a semipermeable membrane that is permeable for air and non-permeable for liquid.

By the wording "member" preferably a component or part of the fluidic cartridge is meant. Preferably, the wording "member" does not mean a section of a component or part of the fluidic cartridge.

The fluidic cartridge is based at least partially on the idea that testing and/or detection of analytes within detection chambers may be sensitive to unwanted components present in the detection chamber. It has been found, for example, that air present in the detection chamber may have a negative or unwanted influence on certain tests. For example, air may have an unwanted or negative influence on a signal-to-noise ratio of a certain test which may result in a less accurate or even erroneous test result. The fluidic cartridge of the present invention therefore suggests the use of a venting chamber fluidly connected to the detection chamber. The venting chamber is configured for venting the detection chamber, in particular for venting air which may be present in the detection chamber and/or introduced into the detection chamber, e.g. during inflow of fluid into the detection chamber. With the help of the venting chamber air can be vented from the detection chamber. For this, the venting chamber includes a semipermeable membrane. The semipermeable membrane allows air to permeate through the membrane but does not allow liquid to permeate through the membrane. As a result, air may leave the detection chamber via the semipermeable membrane of the venting chamber, but liquid is blocked by the semipermeable membrane. Less air in the detection chamber can have a positive effect on a signal-to-noise ratio of a certain test. Thus, sample testing can become more accurate and less prone to errors.

Preferably, the venting chamber is arranged downstream of the detection chamber. This way, air can be moved through the detection chamber and into the venting chamber where it is then vented to the environment. Preferably, the analyte detection includes multiple detection chambers and multiple venting chambers. Preferably, each detection chamber is fluidly connected to a respective venting chamber. Alternatively, some of the multiple detection chambers may be fluidly connected to a single venting chamber.

Preferably, the analyte detection member is a molded part, in particular an injection-molded part. The analyte detection member may be a separate part or a standalone part. The analyte detection member may be insertable into the fluidic cartridge, for example during assembly of the fluidic cartridge.

Preferably, the fluidic cartridge further includes a foil configured for covering one or more detection chambers. Preferably, the foil is transparent and/or translucent. In particular, the foil may be configured for permitting illumination of one or more of the detection chambers, and/or for the detection of visible and/or ultraviolet light therethrough. Preferably, the illumination and/or detection of visible and/or ultraviolet light serves for identifying the presence of one or more analytes in the detection chamber(s), in particular for identifying the presence of amplified genetic material present in the analyte(s).

Preferably, the foil is configured for adhering to the analyte detection member. Preferably, adhering is such that fluidic pathways present in the analyte detection member may be fluidly sealed by the foil. This prevents any mixing of fluids provided in the fluidic pathways of the analyte detection member.

Preferably, the foil and the semipermeable membrane are arranged on opposite sides of the analyte detection member. For example, the semipermeable membrane may be provided on a first side, e.g. a bottom side, of the analyte detection member, and the foil may be provided on a second side, e.g. a top side, of the analyte detection member. Preferably, the foil and semipermeable membrane are arranged directly opposite to one another.

Preferably, when viewed in a cross-sectional view of the cartridge, preferably a vertical cross section, the foil and the semi-permeable membrane at least partially overlap one another, preferably such that, for example, the detection chamber is closed from above/below the analyte detection member by the foil and from below/above the analyte detection member by the semi-permeable membrane.

Preferably, the foil, the semipermeable membrane and the analyte detection member may be preassembled, for example prior to being inserted into the fluidic cartridge.

Preferably, the detection chamber includes a fluid inflow section. The fluid inflow section is configured for retarding a flow of fluid. The fluid inflow section may avoid a spill-over of fluid flowing into the detection chamber. The fluid inflow section may be an enlarging section, preferably enlarging in the direction of fluid flow. The fluid inflow section may have a triangular and/or funnel-like cross-sectional shape. The fluid inflow section may be formed in a portion of a fluidic pathway of the analyte detection member.

Preferably, each fluidic pathway connecting the fluid inlet section with a respective detection chamber has substantially the same length. Moreover, each fluidic pathway connecting a respective detection chamber with a respective venting chamber may have substantially the same length. Thus, fluidic pathways connecting the fluid inlet section with a respective venting chamber may have the same lengths. The same lengths ensure an equal filling of the detection chambers with about the same volume of liquid over the same time.

Preferably, the fluidic cartridge further comprises a first member and a second member. The first and/or the second member may be a molded part, in particular an injection-molded part. The first member and the second member may be formed by the same material or by a different material than the analyte detection member. Various fluidic pathways may be arranged in the first and/or the second member. The analyte detection member may be arranged between the first member and the second member. The semipermeable membrane may be arranged between the first member and the analyte detection member. The foil may be arranged between the second member and the analyte detection member. The first member may be a bottom member of the fluidic cartridge and the second member may be a top member of the fluidic cartridge, but not necessarily. Preferably, the fluidic cartridge further comprises a sealing layer arranged between the first member and the second member. The sealing layer may include or function as a sealing gasket of the fluidic cartridge. The sealing layer may be configured for sealing fluidic pathways arranged in the first and/or second member. The sealing layer may be arranged on a top side of the analyte detection member and/or may at least partially cover the analyte detection member. The sealing layer may be clamped between the first and the second member. The sealing layer may be in a pretensioned and/or compressed state, in particular when being clamped between the first and the second member.

Preferably, at least one of the first member, the second member, the sealing member, the analyte detection member, the foil and/or the semipermeable membrane may include a positioning section for positioning the respective component in a predetermined position to the other component(s). The positioning section ensures a reliable and correct assembly of the fluidic cartridge.

Preferably, the sealing layer includes a cut-out overlapping at least partially with at least one of the detection chambers.

Preferably, the second member includes a second cut-out overlapping at least partially with the cut-out of the sealing layer. Preferably, the second cut-out may also overlap with the fluid inlet section and/or the one or more venting chambers of the analyte detection member. In other words, the fluid inlet section and/or the one or more venting chambers may be covered by the sealing layer but not by the second member of the fluidic cartridge.

Preferably, the analyte detection member further includes a fluid distribution chamber for distributing fluid from the fluid inlet section to the respective detection chamber. Preferably, the foil is configured to be pressed into the fluid distribution chamber. Pressing the foil into the fluid distribution chamber may interrupt a fluid connection between the fluid distribution chamber and the respective detection chamber. In other words, pressing the foil into the fluid distribution chamber fluidly seals the fluid distribution chamber. This may prevent mixing of analytes from the various detection chambers. Preferably, the foil is configured for adhering to the fluid distribution chamber. Preferably, the foil is configured for adhering to the fluid distribution chamber when the foil is pressed into the fluid distribution chamber, preferably wherein adhering to the fluid distribution chamber interrupts a fluid connection between the fluid distribution chamber and the respective detection chamber.

In other words, the foil may be coated with a pressure sensitive adhesive. The pressure sensitive adhesive may be provided at least along a section of the foil facing towards and/or overlapping with the fluid distribution chamber. This may allow occlusion of the fluid distribution chamber by pressing the foil into the fluid distribution chamber. However, the pressure sensitive adhesive may also be provided along other sections of the foil facing towards the analyte detection section, or the entire surface of the foil facing towards the analyte detection section may be coated with the pressure sensitive adhesive. This may facilitate assembly of the cartridge.

Preferably, the foil is configured to be pressed into a respective venting chamber associated with a respective detection chamber. Pressing the foil into the respective venting chamber may interrupt a fluid connection between the respective venting chamber and an environment of the fluidic cartridge. In other words, pressing the foil into the respective venting chamber fluidly seals the respective venting chamber against an environment of the fluidic cartridge. This way, any leakage of analytes, such as amplicons, via the venting chamber may be prevented.

Preferably, the foil is configured to be pressed into the fluid distribution chamber and/or into the respective venting chamber by one or more actuators. The one or more actuators may be external to the fluidic cartridge and/or may be controlled or controllable, e.g. by an apparatus into which the fluidic cartridge is inserted or insertable.

Preferably, the fluidic cartridge further includes a pumping device configured for pumping a liquid into the analyte detection member such that the one or more detection chambers and/or the one or more venting chambers are filled with the liquid whereby air is forced through the semipermeable membrane. Preferably, the pumping device is arranged in and/or controlled by an apparatus into which the fluidic cartridge is inserted or insertable.

Preferably, the fluidic cartridge is configured for the detection chamber to be heated for amplifying an analyte therein, in particular for amplifying genetic material of a target analyte therein. Amplification may be done by means of PCR and/or LAMP (loop-mediated isothermal amplification) and/or any other suitable amplification technique known to a person skilled in the art.

Further embodiments and aspects of the present invention are explained using the accompanying schematic figures, which are incorporated herein and constitute a part of the specification. These figures are merely exemplary. They are not to be understood as limiting the scope of the present disclosure.

FIG 1 is a top view of an exemplary fluidic cartridge in which the invention may be provided.

FIG 2 is a schematic view of an analyte detection member provided in the fluidic cartridge of FIG 1.

FIG 3 is a detailed view of the analyte detection member of FIG 2.

FIG 4 is an exploded view showing the analyte detection member of FIG 2 with a foil and a semipermeable membrane arranged on opposite sides of the analyte detection member.

FIG 5 is an exploded view of the fluidic cartridge of FIG 1.

FIG 6 is a schematic section view of the fluidic cartridge of FIG 5.

FIG 7 is a schematic section view of the arrangement of FIG 6, wherein a sealing layer of the fluidic cartridge is actuated by actuators. Within the figures, same components are referenced by the same reference numerals.

Embodiments of the invention will now be described in context with an exemplary fluidic cartridge in which the invention is implemented.

FIG 1 shows a top view of an exemplary fluidic cartridge 10. Exemplary fluidic cartridge 10 chosen to illustrate the present invention is used for the detection of Chlamydia trachomatis bacterium and/or Neisseria gonorrhoeae bacterium. The person skilled in the art would understand, however, that fluidic cartridge 10 can be used for various other applications using other sample analysis and/or other tests. For example, the fluidic cartridge 10 may be used in any test for amplifying genetic material, such as DNA and/or RNA amplification. The fluidic cartridge 10 may be used, e.g., in polymerase chain reaction (PCR), ligase chain reaction (LCR), transcription-mediated amplification (TMA), loop-mediated isothermal amplification (LAMP), or any other technique making use of a fluidic cartridge.

Fluidic cartridge 10 is multi-part component and predominantly made of plastic material. By the word plastic is meant an organic material which can be shaped when soft and hardened after shaping. Fluidic cartridge 10 is preferably made of a moldable plastic material, more precisely of an injection-moldable plastic material. Exemplary materials can be, for example, polyethylene, polypropylene or polycarbonate. The person skilled in the art would understand, however, that other suitable materials can be used as well.

Fluidic cartridge 10 is intended to be a single-use, disposable cartridge. Fluidic cartridge 10 is intended to be used for performing tests on a sample, especially a liquid sample, introduced into the cartridge 10. Fluidic cartridge 10 is a multiplexed cartridge and primarily intended to be used for point of care testing using, for example, PCR amplification of certain target nucleic acid(s) such as DNA or RNA.

Fluidic cartridge 10 includes a sample entry port 12 configured for receiving a sample. By sample is meant the composition which is introduced into the cartridge 10 to perform the required test(s) or analysis. More precisely, by sample is meant the composition in which it is determined whether the target nucleic acid(s) of interest is/are present. The sample may in particular be a liquid sample. The sample can have a variety of sources such as blood, urine, saliva, swab eluate or other sources. The sample can be pretreated prior to being introduced into cartridge 10. The preferred use of fluidic cartridge 10 is, however, the use of a sample which has not been pretreated prior to introduction into cartridge 10.

The sample is placed on sample entry port 12 from where the sample is introduced into a network 14 of fluidic pathways of cartridge 10. Sample entry port 12 can be closed by a sample cover 16. In the specific embodiment shown, sample cover 16 is bendable and flexible so that sample cover 16 can be bent over sample entry port 12 for closing sample entry port 12 once the sample has been placed on sample entry port 12. In other embodiments not shown, sample cover 16 may be any other appropriate sample cover. For example, sample cover 16 may be a screw cap which can be screwed onto sample entry port 12 for closing the same.

When the sample is introduced into cartridge 10 a variety of actions can be performed on the sample. Some of these actions are described further below.

The sample may be pumped through the fluidic network 14 of cartridge 10. Pumping of the sample, or more generally pumping of a liquid, is performed using one or more pumps, e.g. one or more diaphragm pumps 18. Diaphragm pumps 18 may include a functional layer which is actuated, for example externally, so that a pumping force can be applied to the fluid inside the fluidic network 14.

To perform the necessary actions on the sample, additional liquids may be required. These liquids need to be introduced into the cartridge 10 so that, for example, the sample may be mixed with these liquids and primed for further actions. Within fluidic cartridge 10, liquids are presented in blisters or liquid containers 20. Liquid containers 20 are configured to contain liquid and expel the liquid into cartridge 10.

As shown in FIG 1, cartridge 10 includes three liquid containers 20. The person skilled in the art would understand, however, that in other embodiments fluidic cartridge 10 may include more or less than three containers 20. A first container 22 includes a binding liquid, also called binding buffer. The binding buffer helps that a specific component of the sample, for example nucleic acid(s) of the sample, can be captured by a capture membrane. A second container 24 includes a wash liquid, also called wash buffer. The wash buffer is used to remove cell debris and/or other unwanted cellular components from the sample and/or components that may inhibit the test reaction. A third container 26 includes an elution liquid, also called elution buffer. The elution buffer is used to elute nucleic acid(s) captured by the capture membrane.

The person skilled in the art would understand, however, that liquid containers 20 are not limited to containing binding buffer, wash buffer or eluate buffer. Liquid containers 20 may contain any suitable liquid.

Fluidic cartridge 10 further includes a capture membrane 28. Capture membrane 28 captures and binds specific nucleic acid(s) of interest but does not capture or bind other undesired cellular components such as proteins or lipids. The principle of binding nucleic acid(s) using a capture membrane is well known to a person skilled in the art which is why no further explanation is given herein. Capture membrane 28 may be made of glass fibers, silica or other suitable material(s).

Fluidic cartridge 10 further includes a waste chamber 30. Waste chamber 30 is fluidly connected to capture membrane 28. Waste chamber 30 is used for accommodating liquid(s) and/or liquid mixtures which are no longer used and/or no longer of interest. For example, waste chamber 30 may contain wash buffer which was used to wash capture membrane 28.

Fluidic cartridge 10 further includes a pre-wet chamber 32. Pre-wet chamber 32 is configured for accommodating fluids such as liquids and gaseous fluids such as air. Pre-wet chamber 32 is fluidly connected to capture membrane 28. Pre-wet chamber 32 can be used for pre-wetting capture membrane 28. Pre-wetting of capture membrane 28 allows residual liquid which is present inside pores of capture membrane 28 to be removed from the membrane 28 for priming the line. For example, after capture membrane 28 was washed with wash buffer and flushed with air, residual liquid may still be present inside pores of capture membrane 28. In the pre-wet step, capture membrane 28 may be flushed with elution buffer such that elution buffer can reach capture membrane 28 and push any remaining air and/or residual liquid into pre-wet chamber 32. Alternatively or additionally, in the pre-wet step the fluidic line up to capture membrane 28 may be primed for further action, e.g. by pushing any air contained therein into the pre-wet chamber 32.

Fluidic cartridge 10 further includes a homogenization chamber 34. Homogenization chamber 34 is configured for accommodating fluids such as liquids and gaseous fluids such as air. Homogenization chamber 34 is fluidly connected to capture membrane 28 downstream of capture membrane 28. Homogenization chamber 34 includes one or more lyophilized reagents. Once the homogenization chamber 34 is filled with a fixed amount of liquid, the lyophilized reagent is reconstituted resulting in a liquid having a defined final concentration. In the exemplary fluidic cartridge 10, liquid with nucleic acid(s) eluted from capture membrane 28 is fed into homogenization chamber 34. The nucleic acid(s) may be specific for Chlamydia trachomatis and/or Neisseria gonorrhoeae. The lyophilized reagent may include reagents, in particular PCR reagents such as polymerase, dNTPs and/or enhancers, which may be used in PCR test reactions, such as Chlamydia trachomatis and/or Neisseria gonorrhoeae test reactions. The PCR reagents may be unspecific to an analyte to be tested for.

In other words, when the homogenization chamber 34 is filled with liquid eluted from the capture membrane 28, the lyophilized reagent is reconstituted and a liquid with a desired final concentration is obtained which can then be used, for example, for PCR reaction tests.

Fluidic cartridge 10 further includes an analyte detection section 36. Analyte detection section 36 is provided in an analyte detection member which will be described in more detail in connection with FIGs 2 to 7.

Analyte detection section 36 includes one or more detection chambers 38. Liquid provided by homogenization chamber 34 is provided to the detection chamber(s) 38 via a fluid inlet section 40. Inside detection chamber(s) 38, a PCR reaction or any other suitable test reaction may take place. For example, in the exemplary fluidic cartridge 10, detection chambers 38 may include PCR primers specific for Chlamydia trachomatis and/or Neisseria gonorrhoeae such that Chlamydia trachomatis and/or Neisseria gonorrhoeae can be tested and/or detected. It will be understood that primers specific to any other analyte of interest may be provided.

In the exemplary fluidic cartridge 10, analyte detection section 36 includes five detection chambers 38. A different primer may be provided in each section. The person skilled in the art would understand, however, that more or less than five detection chambers 38 may be present in detection section 36.

Fluidic cartridge 10 may include further components. For example, fluidic cartridge 10 may include one or more valve sections. Valve sections allow the blocking and/or opening of specific fluidic pathways between various components of the cartridge 10. Valve sections may be active valve sections or passive valve sections. By active valve section is meant that these valve sections are controlled actively, for example by an external actuator. By passive valve section is meant that these valve sections are not actively controlled. Passive valve sections may be, for example, check-valves.

Fluidic cartridge 10 may further include one or more pressure sensors configured for sensing a pressure inside a specific fluidic pathway of cartridge 10.

In the following, exemplary actions performed on a sample that has been introduced into fluidic cartridge 10 are described.

Binding buffer is pumped from the first liquid container 22 into the sample entry port 12 using at least one of the diaphragm pumps 18.

The mixture of sample and binding buffer is pumped and/or drawn through the capture membrane 28 and into the waste chamber 30 using at least one of the diaphragm pumps 18.

Wash buffer is pumped from the second liquid container 24 through the capture membrane 28 and into the waste chamber 30 using one of the diaphragm pumps 18. Elution buffer is pumped and/or drawn through the capture membrane 28 into the homogenization chamber 34, thereby filling the homogenization chamber 34 with a fixed volume of liquid. The liquid contains nucleic acid(s) eluted from capture membrane 28. When the liquid reaches the lyophilized reagent inside the homogenization chamber 34, the lyophilized reagent is reconstituted and a liquid with a defined final concentration is obtained.

The liquid is then distributed to the detection chambers 38 so that a PCR reaction or any other suitable test reaction can take place in the chambers 38.

The above steps are only exemplary steps. Further steps may be possible, such as venting of specific pathways, measuring the pressure inside specific pathways and/or opening and closing valves. Moreover, the above sequence of steps is an exemplary sequence of steps. Different step sequences may be possible depending on the test and analysis to be performed.

Referring to FIG 2, a schematic view of an analyte detection member 42 is shown. Analyte detection member 42 includes fluid inlet section 40 and analyte detection section 36. In the specific embodiment shown, analyte detection member 42 is a separate member of the fluidic cartridge and may be inserted or insertable into the fluidic cartridge, for example during assembly of the cartridge. In the specific embodiment shown, analyte detection member 42 is made of a moldable material, in particular an injection-moldable material. In other embodiments not shown, analyte detection member 42 may be made of any other suitable material.

Analyte detection member 42 includes one or more detection chambers 38. In the specific embodiment shown, analyte detection member 42 includes five detection members 38. The person skilled in the art would understand, however, that in other embodiments not shown, analyte detection member 42 may include any number of detection chambers 38. Detection chambers 38 may include one or more analytes. Analyte(s) may be any suitable analyte(s) specific for the test at hand. For example, in the specific embodiment shown, detection chambers 38 may include PCR primers specific for Chlamydia trachomatis and/or Neisseria gonorrhoeae PCR-tests. It will be understood that detection chambers 38 may include the same or different primers and that the primers may be any suitable primer specific for the relevant test(s).

As can be seen, detection chambers 38 are fluidly connected to fluid inlet section 40 via fluidic pathways arranged inside analyte detection member 42. Fluidic pathway 44 fluidly connects fluid inlet section 40 with a fluid distribution chamber 46. Fluid distribution chamber 46 distributes fluid provided by fluid inlet section 40 to the respective detection chamber 38. Each detection chamber 38 is fluidly connected to fluid distribution chamber 46 via a respective fluidic pathway 48.

Analyte detection member 42 further includes several venting chambers 50. In the specific embodiment shown, each detection chamber 38 is associated with a respective venting chamber 50. In other embodiments not shown, more than one detection chamber 38 may be associated with one venting chamber 50. In the specific embodiment shown, each detection chamber 38 is fluidly connected to a respective venting chamber 50 via a respective fluidic pathway 52.

Each venting chamber 50 is configured for venting a respective detection chamber 38, in particular for venting air or any other gaseous fluid present in the respective detection chamber 38, as will be explained in more detail in connection with FIGs 4 to 7. In the specific embodiment shown, the venting chamber 50 is arranged downstream of the respective detection chamber 38 so that any air or gaseous fluid may be moved from the respective detection chamber 38 downstream to the respective venting chamber 50 and from there to the environment of the fluidic cartridge.

In the specific embodiment shown, each fluidic pathway 48 that connects fluid distribution chamber 46 with a respective detection chamber 38 may have substantially the same length. In addition, each fluidic pathway 52 that connects the respective detection chamber 38 with a respective venting chamber 50 may have substantially the same length. The same lengths of fluidic pathways 48, 52 ensure that detection chambers 38 are equally filled with about the same volume of liquid within the same time due to the same hydraulic pressure within fluidic pathways 48, 52. The person skilled in the art would understand, however, that in other embodiments not shown, only some of the fluidic pathways 48, 52 may have the same length.

Referring to FIG 3, a detailed view of analyte detection member 42 is shown. In the detailed view, fluid distribution chamber 46 is connected to a respective detection chamber 38 via a respective fluidic pathway 48.

As can be seen, detection chamber 38 includes a fluid inflow section 54. Fluid inflow section 54 is configured for retarding a flow of fluid flowing into detection chamber 38. Thus, fluid provided in fluidic pathway 48 may be retarded and/or slowed down by fluid inflow section 54. Fluid inflow section 54 prevents any spill-over of fluid and/or any air bubbles which may be present and/or created, e.g. during inflow of fluid. In the specific embodiment shown, fluid inflow section 54 is an enlarging section enlarging in the direction of fluid flow indicted by arrow 56. In the specific embodiment shown, fluid inflow section 54 includes a funnel-like or triangular shape. In other embodiments not shown, fluid inflow section 54 may have any other suitable shape, design and/or form. In the specific embodiment shown, fluid inflow section 54 is formed in a portion of fluidic pathway 48 and is connected to an outer peripheral rim 58 of a well 60 of detection chamber 38. Thus, fluidic pathway 48 transitions into well 60 via fluid inflow section 54.

It will be understood by a person skilled in the art, that any number of detection chambers 38 may include such a fluid inflow section 54. Thus, one, several or all detection chambers 38 may include fluid inflow section 54.

Referring to FIG 4, an exploded view of analyte detection member 42 together with a foil 62 and a semipermeable membrane 64 arranged on opposite sides of analyte detection member 42 is shown.

Foil 62 is configured for covering analyte detection member 42. Foil 62 is transparent and/or translucent so that illumination of detection chambers 38 and/or detection of light, in particular visible and/or ultraviolet light, through foil 62 is possible. Foil 62 allows identifying the presence of an analyte and in particular the presence of an amplified genetic material of the analyte in the respective detection chamber 38 by means of e.g. PCR or LAMP or any other suitable technique. In the specific embodiment shown, foil 62 includes an adhesive layer configured for adhering to analyte detection member 42. Adhering is such that fluidic pathways arranged in analyte detection member 42 are fluidly sealed against the environment by the foil 62. This way, any mixing of fluids provided in the various fluidic pathways of analyte detection member 42 is prevented.

As mentioned, semipermeable membrane 64 and foil 62 are arranged on opposite sides of analyte detection member 42. Semipermeable membrane 64 is permeable for air and non- permeable for liquid. Thus, air can permeate through semipermeable membrane 64, whereas liquid cannot permeate through semipermeable membrane 64. Semipermeable membrane 64 closes venting chamber 50 against the environment. In the specific embodiment shown, semipermeable membrane 64 closes venting chamber 50 from below analyte detection member 42, whereas foil 62 closes venting chamber 50 from above analyte detection member 42. Thus, air which enters venting chamber 50 may leave venting chamber 50 only via semipermeable membrane 64. Liquid, on the other hand, cannot leave venting chamber 50 as the liquid is blocked by semipermeable membrane 64.

In the specific embodiment shown, the foil 62 and the semipermeable membrane 64 are arranged on opposite sides of the analyte detection member 42. For example, in the embodiment shown, the foil 62 is arranged on a top side of analyte detection member 42 and semipermeable membrane 64 is arranged on a bottom side of analyte detection member 42. However, the arrangement may also be the other way around with the semipermeable membrane 64 the top side and the foil 62 on the bottom side of the analyte detection member 42. An arrangement of the foil 62 and the semipermeable membrane 64 on opposite sides of the analyte detection member 42 may simplify the structure and fabrication of the cartridge. In other embodiments not shown, the foil 62 and the semipermeable membrane 64 may be arranged on the same side (e.g., top or bottom) of the analyte detection member 42. Analyte detection member 42, foil 62 and semipermeable membrane 64 may be preassembled, e.g. prior to insertion into the fluidic cartridge.

Referring to FIG 5, an exploded detailed view of the exemplary fluidic cartridge 10 is shown.

Fluidic cartridge 10 includes a first member 66 and a second member 68. In the specific embodiment shown, first and second members 66, 68 are made of moldable material, in particular injection-moldable material. First and/or second members 66, 68 include - among other things - fluidic pathways for transporting fluid within fluidic cartridge 10. Fluidic cartridge 10 further includes a sealing layer 70. Sealing layer 70 is arranged between first and second member 66, 68 and has the primary function of a sealing gasket. Thus, sealing layer 70 shall seal fluidic pathways arranged in the first and/or second member 66, 68. Sealing layer 70 may be clamped between first and second member 66, 68 and may be made of any suitable material.

Analyte detection member 42 is arranged between first member 66 and sealing layer 70. Semipermeable membrane 64 is arranged between first member 66 an analyte detection member 42. Foil 62 is arranged between analyte detection member 42 and sealing layer 70. This arrangement is only one of many examples. Thus, a person skilled in the art would understand that any other suitable arrangement of the components of fluidic cartridge 10 may be possible.

Foil 62, analyte detection member 42, semipermeable membrane 64, first member 66, sealing gasket 70 and/or second member 68 may include one of more positioning sections for positioning the respective component relative to another component of fluidic cartridge 10. Exemplarily, some position sections of fluidic cartridge 10 are marked by reference numeral 72. The person skilled in the art will understand, however, that more or less than the marked positioning sections may be present in fluidic cartridge 10. Also, there may be further positioning sections not shown in FIG 5 or there may be no positioning section at all. Positioning sections ensure an easy and correct assembly of fluidic cartridge 10. The person skilled in the art will understand, however, that positioning sections are not necessary for a correct assembly of fluidic cartridge 10. As can be seen in FIG 5, sealing layer 70 includes a first cut-out 74. Second member 68 includes a second cut-out 76. First cut-out 74 overlaps with detection chambers 38. Second cut-out 76 overlaps with first cut-out 74 and overlaps with venting chambers 50 and fluid inlet section 40 of analyte detection member 42. Sealing layer 70 and foil 62 include a hole 78 so that fluid provided in one of the fluidic pathways of first and/or second member 66, 68 may enter fluid inflow section 40 via hole 78.

Referring to FIG 6, a schematic section view of fluidic cartridge 10 is shown. Figure 6 shows fluidic cartridge 10 in an assembled state. As can be seen, analyte detection member 42 is arranged between first member 66 and sealing layer 70. Second member 68 is arranged on sealing layer 70. Semipermeable membrane 64 is arranged between first member 66 and sealing layer 70, thus underneath analyte detection member 42. In FIG 6, the transparent foil arranged on top of analyte detection member 42 is not shown for ease of understanding.

In the following, filling and venting of detection chamber 38 will be explained.

Fluidic cartridge 10 includes a pumping device 80. Pumping device 80 is configured for pumping fluid through the fluidic network of fluidic cartridge 10 and into fluid inlet section 40. Pumping device 80 may be one of the diaphragm pumps 18 mentioned in connection with FIG 1. Fluid enters fluid inlet section 40 via holes 78 and reaches fluid distribution chamber 46. Fluid distribution chamber 46 distributes the fluid via fluidic pathway 48 to the respective detection chamber 38. Fluid flows into detection chamber 38 via fluid inflow section 54. Fluid may then flow downstream of detection chamber 38 and into venting chamber 50. Venting chamber 50 includes a through hole 82. Through hole 82 fluidly connects venting chamber 50 with the environment of fluidic cartridge 10. Through hole 82 is covered by semipermeable membrane 64. Semipermeable membrane 64 is permeable for air and non-permeable for liquid. Hence, when the fluid enters venting chamber 50, any air contained in the fluid can permeate through semipermeable membrane 64 and leave venting chamber 50, whereas liquid cannot permeate through semipermeable membrane 64 and remains in venting chamber 50. Operation of pumping device 80 may be stopped when all air has passed semipermeable membrane 64. As a result, filling of detection chamber 38 is also stopped. Thus, the semipermeable nature of semipermeable membrane 64 ensures that filling of detection chamber 38 is automatically stopped once all air has passed semipermeable membrane 64 and/or pumping of additional fluid into detection chamber 38 will only be possible against a substantial pressure of the semipermeable membrane 64. The specific operation of pumping device 80 is, however, not the focus of this disclosure which is why no further details on the operation of pumping device 80 is given here.

FIG 6 further shows a heating device 84. Heating device 84 is configured for heating detection chamber 38 so that analytes contained in detection chamber 38 may be heated. Heating device 84 may be any suitable heating device known to a person skilled in the art and may be arranged in any suitable way for heating detection chamber 38. Heating device 84 may be associated with a single detection chamber 38 or with a plurality of detection chambers 38. Heating device 84 may be part of an apparatus into which fluidic cartridge 10 is inserted or insertable. Heating device 84 may be used, for example, in PCR and/or LAMP tests where the genetic target material needs to be amplified at a constant temperature above room temperature. The person skilled in the art will understand, however, that other test may be performed where detection chamber 38 needs to be heated. The person skilled in the art will also understand that there may be tests which do not need heating of detection chamber 38. Thus, heating device 84 is not essential to the use of fluidic cartridge 10 but only optional.

FIG 6 further shows an analyte detection device 86. Analyte detection device 86 is shown schematically and only shown for ease of understanding. Analyte detection device 86 is not essential to the use of fluidic cartridge 10. Analyte detection device 86 may be any suitable detection device known to a person skilled in the art. For example, analyte detection device 86 may be configured for illuminating detection chamber 38 and/or may be configured for receiving and/or analyzing light, e.g. visible and/or ultraviolet light, emitted by the analyte and/or by a genetic target material of the analyte as would be the case, e.g. during amplification of the genetic target material. Analyte detection device 86 may be associated with a single detection chamber 38 or with a plurality of detection chambers 38. Analyte detection device 86 may be part of an apparatus into which fluidic cartridge 10 is inserted or insertable. FIG 6 further shows actuators 88, 90. Actuators 88, 90 are configured for applying a force onto sealing layer 70 and/or the foil arranged underneath sealing layer 70. A first actuator 88 is configured for pressing sealing layer 70 and/or the foil into fluid distribution chamber 46. A second actuator 90 is configured for pressing sealing layer 70 and/or the foil into venting chamber 50. Second actuator 90 may be associated with a single venting chamber 50 or with a plurality of venting chambers 50. Actuators 88, 90 may be external to fluidic cartridge 10 and/or may be part of an apparatus into which fluidic cartridge 10 is inserted or insertable.

Referring to FIG 7, fluidic cartridge 10 is shown wherein sealing layer 70 is pressed into fluid distribution chamber 46 and into venting chamber 50 by actuators 88, 90, as indicated by the dashed lines. When actuator 88 applies a pressing force onto sealing layer 70, the foil arranged underneath the sealing layer 70 is pressed into fluid distribution chamber 46. Fluid distribution chamber 46 is sealed and a fluid connection between fluid distribution chamber 46 and a respective detection chamber 38 is interrupted. Sealing the fluid distribution chamber 46 prevents any mixing of analytes from the various detection chambers 38. When actuator 90 applies a pressing force onto sealing layer 70, the foil underneath the sealing layer 70 is pressed into the respective venting chamber 50. As a result, the respective venting chamber 50 is fluidly sealed against the environment and a fluid connection between the respective venting chamber 50 and the environment of fluidic cartridge 10 is interrupted. Sealing the venting chambers 50 prevents any leakage of analytes, e.g. amplicons, to the environment. Sealing of fluid distribution chamber 46 and/or sealing of venting chamber 50 is, however, not essential to the use of fluidic cartridge 10.

In the specific embodiment shown, fluid distribution chamber 46 and/or venting chamber 50 are sealed by press sealing layer 70 and therewith the foil into fluid distribution chamber 46 and venting chamber 50. A person skilled in the art will understand, however, that in other embodiments not shown, fluid distribution chamber 46 and/or venting chamber 50 may be sealed pressing only the foil into fluid distribution chamber 46 and/or venting chamber 50. In other words, in other embodiments not shown, there may be no sealing layer 70 arranged between actuators 88, 90 and the foil. Thus, actuators 88, 90 may directly act on the foil. Providing sealing layer 70 on top of the foil is thus not essential to the use of fluidic cartridge 10. However, using the sealing layer 70 on top of the foil may ensure a more even pressing of the foil, may ensure that the foil tightly conforms to the shape of the fluid distribution chamber 46 and/or venting chamber 50, and/or may mitigate potential damage of the foil caused by actuators 88, 90 acting directly on the foil.

The following aspects are preferred embodiments of the invention:

1. A fluidic cartridge (10), comprising: an analyte detection member (42) including a fluid inlet section (40), and an analyte detection section (36) fluidly connected to the fluid inlet section (40), wherein the analyte detection section (36) includes a detection chamber (38), and a venting chamber (50) fluidly connected to the detection chamber (38), wherein the venting chamber (50) is at least partially closed by a semipermeable membrane (64) that is permeable for air and non-permeable for liquid.

2. The fluidic cartridge (10) of aspect 1, wherein the venting chamber (50) is arranged downstream of the detection chamber (38).

3. The fluidic cartridge (10) of any one of the preceding aspects, wherein the analyte detection member (42) is a molded part, preferably an injection molded part.

4. The fluidic cartridge (10) of any one of the preceding aspects, further comprising: a foil (62) configured for covering the detection chamber (38), preferably wherein the foil (62) is transparent or translucent, more preferably wherein the foil (62) is configured for permitting illumination of the detection chamber (38) and/or detection of visible and/or ultraviolet light therethrough, preferably wherein the illumination and/or detection serves for identifying the presence of an analyte in the detection chamber (38), more preferably wherein the analyte comprises an amplified genetic material.

5. The fluidic cartridge (10) of aspect 4, wherein the foil (62) is configured for adhering to the analyte detection member (42), preferably wherein adhering is such that fluidic pathways (44, 48, 52) arranged in the analyte detection member (42) are fluidly sealed by the foil (62).

6. The fluidic cartridge (10) of any one of aspects 4-5, wherein the foil (62) and the semipermeable membrane (64) are arranged on opposite sides of the analyte detection member (42), preferably directly opposite to one another.

7. The fluidic cartridge (10) of any one of the preceding aspects, wherein the detection chamber (38) includes a fluid inflow section (54), the fluid inflow section (54) being configured for retarding a flow of fluid flowing into the detection chamber (38).

8. The fluidic cartridge (10) of aspect 7, wherein the fluid inflow section (54) is an enlarging section, preferably enlarging in the direction of fluid flow, preferably wherein the fluid inflow section (54) includes a triangular or funnel-like cross-sectional shape.

9. The fluidic cartridge (10) of any one of the preceding aspects, wherein the analyte detection member (42) includes multiple detection chambers (38) and multiple venting chambers (50) and each detection chamber (38) is fluidly connected to a respective venting chamber (50).

10. The fluidic cartridge (10) of aspect 9, wherein each fluidic pathway (48) connecting the fluid inlet section (40) with a respective detection chamber (38) has substantially the same length, and/or each fluidic pathway (48, 52) connecting the fluid inlet section (40) with a respective venting chamber (50) has substantially the same length.

11. The fluidic cartridge (10) of any one of the preceding aspects, further comprising: a first member (66), and a second member (68), wherein the analyte detection member (42) is arranged between the first member (66) and the second member (68), preferably wherein the semipermeable membrane (64) is arranged between the analyte detection member (42) and the first member (66).

12. The fluidic cartridge (10) of aspect 11, further comprising: a sealing layer (70) arranged between the first member (66) and the second member (68), wherein the sealing layer (70) is arranged on top of the analyte detection member (42).

13. The fluidic cartridge (10) of aspect 12, wherein the sealing layer (70) includes a cutout (74) overlapping at least partially with a respective detection chamber (38).

14. The fluidic cartridge (10) of aspect 13, wherein the second member (68) includes a second cut-out (76) overlapping at least partially with the cut-out (74) of the sealing layer (70).

15. The fluidic cartridge (10) according to any of aspects 4-14, wherein the analyte detection member (42) includes a fluid distribution chamber (46) configured for distributing fluid from the fluid inlet section (40) to a respective detection chamber (38), wherein the foil (62) is configured to be pressed into the fluid distribution chamber (46), preferably wherein pressing the foil (62) into the fluid distribution chamber (46) interrupts a fluid connection between the fluid distribution chamber (46) and the respective detection chamber (38).

16. The fluidic cartridge of aspect 15, wherein the foil (62) is configured to be pressed into the fluid distribution chamber (46) by an actuator (88) external to the fluidic cartridge (10).

17. The fluidic cartridge (10) according to any of aspects 4-16, wherein the foil (62) is configured to be pressed into a respective venting chamber (50), preferably wherein pressing the foil (62) into the respective venting chamber (50) interrupts a fluid connection between the respective venting chamber (50) and the environment of the fluidic cartridge (10).

18. The fluidic cartridge (10) of aspect 17, wherein the foil (62) is configured to be pressed into the respective venting chamber (50) by an actuator (90) external to the fluidic cartridge (10).

19. The fluidic cartridge (10) of aspects 15-18, preferably in combination with aspect 5, wherein the foil (62) is configured to adhere to the fluid distribution chamber (46) and/or the respective venting chamber (50) when the foil (62) is pressed into the fluid distribution chamber (46) and/or the respective venting chamber (50), respectively.

20. The fluidic cartridge (10) of any one of the preceding aspects, further comprising: a pumping device (80) configured for pumping liquid into the analyte detection member (42) such that the detection chamber (38) and/or the venting chamber (50) is filled with the liquid, whereby air contained in the venting chamber (50) is forced through the semipermeable membrane (64) out of the venting chamber (50).

21. The fluidic cartridge (10) of any one of the preceding aspects, wherein the fluidic cartridge (10) is configured for the detection chamber (38) to be heated for amplifying an analyte therein, preferably for amplifying genetic material of a target analyte by means of PCR or LAMP.

Claims

1. A fluidic cartridge (10), comprising: an analyte detection member (42) including a fluid inlet section (40), and an analyte detection section (36) fluidly connected to the fluid inlet section (40), wherein the analyte detection section (36) includes a detection chamber (38), and a venting chamber (50) fluidly connected to the detection chamber (38), wherein the venting chamber (50) is at least partially closed by a semipermeable membrane (64) that is permeable for air and non-permeable for liquid, and a foil (62) configured for covering the detection chamber (38), wherein the foil (62) is transparent or translucent and configured for permitting illumination of the detection chamber (38) and/or detection of visible and/or ultraviolet light therethrough, and wherein the foil (62) and the semipermeable membrane (64) are arranged on opposite sides of the analyte detection member (42).

2. The fluidic cartridge (10) of claim 1, wherein the venting chamber (50) is arranged downstream of the detection chamber (38).

3. The fluidic cartridge (10) of any one of the preceding claims, wherein the illumination and/or detection serves for identifying the presence of an analyte in the detection chamber (38), preferably wherein the analyte comprises an amplified genetic material.

4. The fluidic cartridge (10) of any of the preceding claims, wherein the foil (62) is configured for adhering to the analyte detection member (42), preferably wherein adhering is such that fluidic pathways (44, 48, 52) arranged in the analyte detection member (42) are fluidly sealed by the foil (62).

5. The fluidic cartridge (10) of any one of the preceding claims, wherein the detection chamber (38) includes a fluid inflow section (54), the fluid inflow section (54) being configured for retarding a flow of fluid, preferably wherein the fluid inflow section (54) is an enlarging section, preferably enlarging in the direction of fluid flow, preferably wherein the fluid inflow section (54) includes a triangular or funnel-like cross-sectional shape.

6. The fluidic cartridge (10) of any one of the preceding claims, wherein the analyte detection member (42) includes multiple detection chambers (38) and multiple venting chambers (50) and each detection chamber (38) is fluidly connected to a respective venting chamber (50).

7. The fluidic cartridge (10) of claim 6, wherein each fluidic pathway (48) connecting the fluid inlet section (40) with a respective detection chamber (38) has substantially the same length, and/or each fluidic pathway (48, 52) connecting the fluid inlet section (40) with a respective venting chamber (50) has substantially the same length.

8. The fluidic cartridge (10) of any one of the preceding claims, further comprising: a first member (66), and a second member (68), wherein the analyte detection member (42) is arranged between the first member (66) and the second member (68), preferably wherein the semipermeable membrane (64) is arranged between the analyte detection member (42) and the first member (66).

9. The fluidic cartridge (10) of claim 8, further comprising: a sealing layer (70) arranged between the first member (66) and the second member (68), wherein the sealing layer (70) is arranged on top of the analyte detection member (42).

10. The fluidic cartridge (10) of claim 9, wherein the sealing layer (70) includes a cut-out (74) overlapping at least partially with a respective detection chamber (38).

11. The fluidic cartridge (10) according to any of the preceding claims, wherein the analyte detection member (42) includes a fluid distribution chamber (46) configured for distributing fluid from the fluid inlet section (40) to a respective detection chamber (38), wherein the foil (62) is configured to be pressed into the fluid distribution chamber (46), preferably wherein pressing the foil (62) into the fluid distribution chamber (46) interrupts a fluid connection between the fluid distribution chamber (46) and the respective detection chamber (38).

12. The fluidic cartridge (10) according to any of the preceding claims, wherein the foil (62) is configured to be pressed into a respective venting chamber (50), preferably wherein pressing the foil (62) into the respective venting chamber (50) interrupts a fluid connection between the respective venting chamber (50) and the environment of the fluidic cartridge (10).

13. The fluidic cartridge (10) of any one of the preceding claims, further comprising: a pumping device (80) configured for pumping liquid into the analyte detection member (42) such that the detection chamber (38) and/or the venting chamber (50) is filled with the liquid, whereby air contained in the venting chamber (50) is forced through the semipermeable membrane (64) out of the venting chamber (50).

14. The fluidic cartridge (10) of any one of the preceding claims, wherein the fluidic cartridge (10) is configured for the detection chamber (38) to be heated for amplifying an analyte therein, preferably for amplifying genetic material of a target analyte by means of PCR or LAMP.

15. The fluidic cartridge (10) of any one of the preceding claims, wherein the foil (62) is configured to adhere to the fluid distribution chamber (46) when the foil (62) is pressed into the fluid distribution chamber (46); and/or wherein the foil (62) is configured to adhere to the venting chamber (50) when the foil (62) is pressed into the venting chamber (50).