Liquid handling and processing tool for analyzing biological samples - Patents.com
The modular liquid handling tool addresses leakage and cross-contamination issues by using a rotatable valve system with sealing plates to maintain chamber integrity and enable easy handling, ensuring safe and efficient biological sample processing.
Patent Information
- Application Number
- JP2021576454
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2019-07-18
- Filing Date
- 2020-07-17
- Publication Date
- 2025-01-14
- Estimated Expiration
- 2040-07-17
AI Technical Summary
Existing liquid handling cartridges for biological samples face issues with safe operation and handling, as they can leak if tipped or dropped, and are difficult to transport due to the need for opening compartments to add reagents, leading to potential cross-contamination.
A modular liquid handling and processing tool with a rotatable valve body and sealing plates that allows controlled fluid connections and ventilation, ensuring chambers remain sealed unless accessed, and includes interfaces for external modules, enabling easy handling and preventing cross-contamination.
The tool ensures safe and secure handling of biological samples by maintaining chamber integrity, preventing leaks and cross-contamination, and facilitating easy manipulation even after filling, with modular design allowing complex tasks through dedicated chamber functions and external module integration.
Smart Images

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Abstract
Description
[Technical field]
[0001] The present invention relates to a liquid handling and processing tool for analyzing biological samples. Furthermore, the present invention relates to a fluid processing and detection module for processing a liquid sample and detecting an analyte in the sample. [Background technology]
[0002] The need for safe operation and performance of bioanalytical assays has led to the development of integrated cartridge-based tests. Typically, such cartridges contain all the reagents required to perform the respective test and provide compartments for performing dedicated processing and detection steps. In recent years, disposable cartridges have been developed to perform the analysis of biological samples for various diagnostic and monitoring purposes. One aspect of cartridge-based tests is that the entire process is self-contained. The sample or reagents never come into contact with the instrument used to process the cartridge. An early basic design of a liquid handling cartridge is outlined in U.S. Pat. No. 4,231,990. A basic architecture that arranges valves around a centrally located fluid displacement unit and a single fluid sample processing chamber is disclosed in WO 02 / 18902 A1. WO 03 / 072253 A1 describes a cartridge following the basic design of WO 02 / 18902 A1, with additional sample processing means housed in one of the chambers in the housing. However, the references do not outline in detail how a safe operation of the system can be ensured without contaminating the reagents and devices contained in each chamber. US Pat. No. 9,394,086 describes a lid for sealing such devices of WO 02 / 18902 A1 and WO 03 / 072253 A1. The lid of US Pat. No. 9,394,086 seals all chambers during transport. Before use, the lid is opened, the sealing is irreversibly broken and removed, and the cartridge is no longer sealed. It can therefore only be operated in an upright position. After breaking the seal, the cartridge may leak if dropped or tipped over. Once filled, each cartridge is difficult to transport or handle, because each compartment is essentially opened to be filled with the required reagent. Summary of the Invention [Problem to be solved by the invention]
[0003] The present invention aims to avoid or overcome the disadvantages associated with the prior art. [Means for solving the problem]
[0004] In a first aspect, the present invention relates to a liquid handling and processing tool (1) for analyzing biological samples, said tool comprising: A valve body (2) including a fluid displacement chamber (21), said fluid displacement chamber having a top (211) and a bottom (212) and an opening (2111) at the top and an opening (2121) at the bottom, respectively, said fluid displacement chamber allowing for aspirating liquid therefrom and expelling liquid therefrom, said valve body further including a first sealing plate (2112) at the top and a second sealing plate (2121) at the bottom, said first sealing plate at the top and said opening (2121) at the bottom being spaced apart from each other by a first sealing plate (2112) at the top and a second sealing plate (2121) at the bottom. a valve body (2) fixedly coupled to one another via the fluid displacement chamber, each of the first and second sealing plates having a port (21121, 21211), the fluid displacement chamber being fluidly connected to the port of the second sealing plate via a channel (21212) in the second sealing plate, the channel extending from the opening (2121) of the fluid displacement chamber at the bottom and terminating in the port (21211) of the second sealing plate; 1. A housing (3) having a plurality of chambers (31, 31', 31'', 31''') for holding reagents or receiving liquids, each of said chambers having a top (311) and a bottom (312), respectively, a fluid port (3121) at said bottom, and optionally a vent port (3111) at said top, said housing further comprising at least one interface (32) for fluidly connecting a separate fluid processing module to said housing, said at least one interface including a single port (321). wherein the valve body and housing are arranged in such a manner that the fluid displacement chamber is located within the housing, the valve body is rotatable within the housing, the first sealing plate seals the plurality of chambers at their respective tops and the second sealing plate seals the plurality of chambers at their respective bottoms, and the valve body is configured to establish a single fluid connection from the fluid displacement chamber through the channel and through the port of the second sealing plate to a selected one of the plurality of chambers and optionally allow simultaneous venting of the same or another chamber through the port of the first sealing plate, or the valve body is configured to establish a single fluid connection from the fluid displacement chamber through the channel and through the port of the second sealing plate to the at least one interface and any separate fluid treatment module attached to such interface, if present.
[0005] In a further aspect, the present invention relates to a liquid handling and processing tool (1) for analyzing biological samples, in particular a liquid handling and processing tool as described in the preceding paragraph, said tool comprising: A valve body (2) having a longitudinal axis and including a fluid displacement chamber (21) along the longitudinal axis, said fluid displacement chamber having a top (211) and a bottom (212) and an opening (2111) at the top and an opening (2121) at the bottom, respectively; the fluid displacement chamber further comprising a piston (213) movable within the fluid displacement chamber and enabling the drawing of liquid into the fluid displacement chamber and the expulsion of liquid from the fluid displacement chamber; the fluid displacement chamber is centrally located within the valve body and aligned along the longitudinal axis of the valve body; The valve body (2) further includes a first circular sealing plate (2112) located at the top of the fluid displacement chamber and a second circular sealing plate (2121) located at the bottom of the fluid displacement chamber; the first circular sealing plate (2112) is fixedly connected to the valve body at the top of the fluid displacement chamber and has a vent port (21121) located off-center of the first circular sealing plate, the first circular sealing plate allowing access to the opening (2111) of the fluid displacement chamber at the top by an opening (21122) in the first circular sealing plate, preferably a central opening, that is aligned with the opening (2111) at the top of the fluid displacement chamber; the second circular sealing plate (2121) is fixedly connected to the valve body at the bottom of the fluid displacement chamber and has a fluid port (21211) located off-center of the second circular sealing plate, the second circular sealing plate allowing access to the opening (2121) of the fluid displacement chamber at the bottom by an opening (21213) in the second circular sealing plate, preferably a central opening, that is aligned with the opening (2121) at the bottom of the fluid displacement chamber; the vent ports (21121) of the first circular sealing plate and the fluid ports (21211) of the second circular sealing plate are aligned with one another; a valve body (2) wherein the second circular sealing plate further comprises a channel (21212) extending radially from the opening (21213) in the second circular sealing plate and terminating in the fluid port (21211) located off-center of the second circular sealing plate, the valve body thus being configured to establish a single fluid connection with the fluid port located off-center of the second circular sealing plate via the channel; 1. A housing (3) comprising a plurality of chambers (31, 31', 31'', 31''') for holding reagents or receiving liquids, said chambers being arranged around a central hollow space, each of said chambers having a top (311) and a bottom (312), respectively, a fluid port (3121) at said bottom, and optionally a vent port (3111) at said top, said housing further comprising at least one interface (32) for fluidly connecting a separate fluid processing module to said housing, said at least one interface comprising a single port (321). wherein the valve body and housing are arranged in such a manner that said fluid displacement chamber is located within said central hollow space, the valve body being rotatable within said central hollow space about said longitudinal axis, a first circular sealing plate of said valve body seals said plurality of chambers at their respective tops and a second circular sealing plate of said valve body seals said plurality of chambers at their respective bottoms, and the valve body is configured to establish a single fluid connection from said fluid displacement chamber to a selected one of a plurality of chambers via said channel and via a fluid port at a bottom of said second circular sealing plate, and optionally to allow simultaneous venting of the same or another chamber via a vent port of said first circular sealing plate, or the valve body is configured to establish a single fluid connection from said fluid displacement chamber to said at least one interface and any separate fluid treatment module attached to such interface, if present, via said channel and via a fluid port at a bottom of said second circular sealing plate.
[0006] In one embodiment, the ports of the first and second sealing plates are aligned with one another along a longitudinal axis of the valve body.
[0007] In one embodiment, at least one chamber of the plurality of chambers has a vent port (3111) at its top, and preferably each of the plurality of chambers has a vent port at its respective top.
[0008] In one embodiment, the multiple chambers are closed at the top by a single lid (313) with any vent ports (3111), if present, located therein.
[0009] In one embodiment, at least one of the plurality of chambers further comprises a loading port (3112) for adding liquid to the chamber, the loading port being located at the top of the at least one chamber, the loading port, if present, being different from the vent port.
[0010] In one embodiment, some, and preferably all, of the plurality of chambers each have a loading port (3112) for adding liquid to the respective chamber, the loading port being located at the top of the respective chamber, and the loading port being distinct from any vent port, if present.
[0011] In one embodiment, the loading ports are located in a single lid (313).
[0012] In one embodiment, the housing includes a number of interfaces (32, 32', 32'') for fluidly connecting individual fluid treatment modules to the housing, each of the number of interfaces including a single port (321, 321', 321''').
[0013] In one embodiment, at least one chamber is a compartmentalized chamber having different compartments (314, 314', 314'') fluidly connected to each other and such compartments are configured to perform different functions such as filtration, serving as a reservoir for processing fluids or serving as an overflow volume, or at least two chambers of said plurality of chambers are fluidly connected to each other and each of such at least two chambers is configured to perform different functions such as filtration, serving as a reservoir for processing fluids or serving as an overflow volume, preferably said at least two chambers are fluidly connected to each other and each has a fluid port at the bottom and a vent port at the top.
[0014] In one embodiment, the channel (21212) has no other openings other than the opening (2121) of the fluid displacement chamber at the bottom and the port (21211) of the second sealing plate, but is otherwise a closed channel.
[0015] In one embodiment, the single port of the at least one interface for fluidly connecting a fluid treatment module to the housing is not part of any of the multiple chambers and is configured to allow attachment of a fluid treatment module or other module to the housing from outside.
[0016] In one embodiment, sealing of the plurality of chambers by the first and second sealing plates is achieved by using a suitable sealing material disposed between the respective plates and the housing, and / or by lining the first and second sealing plates and / or the housing with such a suitable sealing material, and / or by configuring the first and second sealing plates and the housing such that the respective sealing plates are pressed against the housing with sufficient force to seal the plurality of chambers, preferably the suitable sealing material is selected from elastomeric, thermoplastic and other plastic materials.
[0017] In one embodiment, the channel in the second plate comprises: an optical setup capable of detecting the presence, volume and / or optical properties, e.g. visible color, fluorescence, extinction, of any fluid in the channel; A pressure sensor for determining a pressure within said liquid handling and processing tool, preferably within said channel. The device is configured to be interrogated by either
[0018] In one embodiment, the optical setup is a reflective optical setup, e.g. a light barrier, and / or the pressure sensor is a piezo-based pressure sensor.
[0019] In one embodiment, the liquid handling and processing tool further comprises at least one fluid processing module (4) attached to said at least one interface (32) or, if present, to several such interfaces (32, 32', 32'') via said single port (321) of said at least one interface.
[0020] In one embodiment, the fluid processing module is a module configured to perform a nucleic acid amplification reaction, a module configured to concentrate or purify an analyte of interest, e.g., a nucleic acid, or a module for disrupting, homogenizing, and / or lysing a biological sample.
[0021] In one embodiment, the fluid processing module (4) is a module configured to perform a nucleic acid amplification reaction, and the nucleic acid amplification module has an opening (41) whereby the nucleic acid amplification module is fluidly connected to the single port (321) of the interface, preferably the opening is the only opening of the fluid processing module.
[0022] In one embodiment, the fluid treatment module includes a frame (42) enclosing a volume (421) having at least one wall (4211) that is flexible and conformable to an external temperature regulating surface.
[0023] In one embodiment, the fluid treatment module further includes a rigid wall region (4212) that is transparent or otherwise suitable for optical interrogation by an external optical sensor such that the fluid treatment module is configured to enable detection of contents within the fluid treatment module.
[0024] In one embodiment, the fluid treatment module has a bifurcated volume consisting of a first part and a second part, the first part being a first volume directly connected to and in communication with the opening of the fluid treatment module, in which sample processing and optionally detection of a processing reaction occurs, and the second part being a second volume connected only to the first part via a connecting tube but otherwise closed, the second volume being a volume for receiving liquid or gas overflow from the first part and for acting as a pressure accumulator.
[0025] In one embodiment, the first volume has two opposing walls, one of which is formed by the flexible wall (4211) as further defined above or part thereof, and the other of which is formed by the rigid wall region (4212) as further defined above or part thereof.
[0026] In one embodiment, at least one of the plurality of chambers has an outer wall (315) accessible from outside the housing, the outer wall being configured to be contacted by a temperature adjustment device, thereby enabling temperature control within the at least one chamber when the temperature adjustment device contacts the outer wall.
[0027] In a further aspect, the present invention also relates to a fluid treatment and detection module (4) for treating a liquid sample and detecting an analyte in said sample, configured to be used in conjunction with a liquid handling and processing tool (1) as further defined above and configured to be attached to said at least one interface (32) of said liquid handling and processing tool via said single port (321) of said at least one interface, said fluid treatment and detection module (4) comprising: A frame (42) enclosing a volume (421) having at least one wall (4211) that is flexible and conformable to an external temperature regulating surface; a rigid wall region (4212) that is transparent or otherwise suitable for optical interrogation by an external optical sensor; an opening (41) by which the fluid treatment and detection module is fluidly connectable to the single port (321) of the interface (32) of the liquid handling and processing tool, preferably the opening of the fluid treatment and detection module being the only opening of the module; Includes.
[0028] In one embodiment, the fluid processing and detection module according to the invention comprises a bifurcated volume consisting of a first part and a second part, the first part being a first volume directly connected to and in communication with the opening of the fluid processing and detection module, in which sample processing and detection of any processing reaction takes place, and the second part being a second volume connected only to the first part via a connecting tube, but which is otherwise a closed volume, the second part being a volume for receiving liquid or gas overflow from the first part and for acting as a pressure accumulator.
[0029] In one embodiment, the first volume has two opposing walls, one of which is formed by the flexible wall (4211) as further defined above or part thereof, and the other of which is formed by the rigid wall region (4212) as further defined above or part thereof.
[0030] The inventors have devised a device that is a cartridge for analyzing biological samples that is ready to be filled immediately and can be easily handled and operated even after it has been filled, without the risk of cross-contamination between different reagents, liquids or compartments due to the modular structure of the device. More specifically, the independent compartments or chambers in the liquid handling and processing tool are separated from each other, unless otherwise specified. In one embodiment, the chambers of the chambers for holding the reagents or receiving liquids are closed chambers, apart from the presence of a fluid port at the bottom, optionally a vent port at the top and further optionally a loading port at the top of each chamber. The fluid port at the bottom of each and the vent port at the top of each are closed, if present, unless they are addressed by the respective ports of the corresponding sealing plates, i.e. the second sealing plate at the bottom and the first sealing plate at the top. Furthermore, if a chamber has an additional loading port at the top, this is configured so that it can be resealed after use, i.e. after adding a liquid, reagent or sample to the respective chamber. By having separate chambers isolated from one another, and by each chamber being effectively a closed chamber, the liquid handling and processing tool according to the invention allows for the handling and processing of liquids with essentially no risk of cross-contamination. Furthermore, the liquid handling and processing tool according to the invention has no risk of leaking or losing liquid, even if inverted or otherwise removed from its normal upright position.
[0031] According to a first aspect, a liquid handling and processing tool for analyzing biological samples includes a valve body. Such a valve body allows for specific and targeted establishment of a fluid connection from a fluid displacement chamber in the valve body to one of a plurality of chambers in the liquid handling and processing tool. The fluid displacement chamber includes a top and a bottom and an opening at the top and the bottom, respectively. This allows for aspirating liquid from the fluid displacement chamber and expelling liquid. Furthermore, the valve body further includes a first sealing plate at the top and a second sealing plate at the bottom. The two sealing plates are fixedly coupled to each other via the fluid displacement chamber, and each of the first and second sealing plates has a port. The fluid displacement chamber fluidly connects with a port of the second sealing plate at the bottom through a channel in the second sealing plate. The channel extends from the opening of the fluid displacement chamber at the bottom and terminates in the port of the second sealing plate. This channel is typically a closed channel, i.e., accessible only through the opening of the fluid displacement chamber and / or the port of the second sealing plate. The liquid handling and processing tool further includes a housing having a plurality of chambers for holding the receiving liquid reagents, each of these chambers having a top and a bottom. It should be noted that these chambers are typically isolated from each other unless otherwise specified. Likewise, they are also closed chambers in the sense that they are closed, i.e., hermetically sealed, unless addressed through the fluid portion at their respective bottoms and / or optionally, through a vent port at their respective tops, if present. Furthermore, some of the respective chambers may additionally have a loading port at their tops, through which the respective chambers may be loaded or filled with the desired liquid.If such a loading port is present, it is configured to be sealed again after use, i.e. after liquid has been added to or removed from the respective chamber, and such loading port can be closed again, thus closing the respective chamber. Closing of the loading port can occur by any suitable means, e.g. cap, seal or plug. Such cap, seal or plug can be individualized for each respective loading port, or it can be a common sealing ring or cap that closes multiple ports simultaneously. The term "to close" or "closed" as used herein is used synonymously with "to hermetically seal" and "hermetically sealed", meaning that no liquid, fluid or other substance can be added or removed except through any of the specific ports or openings specially provided for that purpose. It is also noted that the channel in the second sealing plate is a closed channel, i.e. liquid can only enter or exit this channel through the opening of said fluid displacement chamber at the bottom or through the port in said second sealing plate. The channel may be manufactured as a "tunnel" in said second sealing plate, or it may be made as a groove and then covered by a suitable cover or lid placed over such groove.
[0032] The liquid handling and processing tool for analyzing biological samples further comprises a housing having a plurality of chambers for holding reagents or receiving liquids, each of the chambers having a top and a bottom, a fluid port at the bottom, and optionally a vent port at the top. Except for the presence of such port at the top and a further optional loading port, each chamber is closed. The housing further comprises at least one interface for fluidly connecting a separate fluid processing module to said housing. It should be noted that such separate fluid processing modules do not form part of the liquid handling and processing tool according to the invention unless specifically indicated. The at least one interface for fluidly connecting the fluid processing modules comprises a single port. The term "fluidly connect" as used herein is meant to refer to a connection that allows the flow of liquids between the two entities then connected without leakage. Such a term may also be used herein as a synonym for a "leak-free" connection.
[0033] In a liquid handling and processing tool for analyzing biological samples, the valve body and the housing are arranged in such a way that the fluid displacement chamber is located in the housing and the valve body is rotatable in the housing. Depending on the position of the respective ports in the valve body and the second sealing plate and the first sealing plate, independent chambers in the plurality of chambers can be addressed by a user, thus enabling the establishment of a connection from the fluid displacement chamber to the respective chamber, thereby enabling the flow of liquid from the fluid displacement chamber to the so addressed chamber or from the so addressed chamber to the fluid displacement chamber. Depending on the position and rotation of the valve body in the housing, different chambers can be addressed, i.e., fluidly connected to the fluid displacement chamber. It should be noted that typically, only one chamber is fluidly connected to the fluid displacement chamber at a time.
[0034] The valve body includes a first sealing plate on the top and a second sealing plate on the bottom, the first sealing plate sealing the multiple chambers at their respective tops and the second sealing plate sealing the multiple chambers at their respective bottoms.
[0035] The first sealing plate of the liquid handling and processing tool seals the chambers at their respective tops, more specifically at the respective vent ports of the top chambers, if present. The second sealing plate seals the chambers at their respective bottoms, more specifically at the respective fluid ports at the bottoms. The valve body is configured to establish a single fluid connection from the fluid displacement chamber to a selected one of the chambers through the channel and through a port in / of the second sealing plate. A "selected chamber" is typically a chamber selected by a user to be addressed by the valve body, i.e., to be fluidly connected to the fluid displacement chamber. The valve body is also optionally configured to allow simultaneous venting of the same chamber (to which a single fluid connection is established through a port in the second sealing plate) or another chamber through a port in the first sealing plate. Whether the same or different chambers are simultaneously vented depends on the presence of a vent port at the top of each chamber and / or the respective alignment of the second sealing plate at the bottom and the first sealing plate at the top. If the ports of the second sealing plate and the ports of the first sealing plate are aligned with each other such that they are aligned along the longitudinal axis of the valve body / fluid displacement chamber, this is a single chamber to which a single fluid connection is established from the fluid displacement chamber at the bottom, and this single chamber is vented simultaneously. However, if the ports in the second sealing plate and the ports in the first sealing plate are offset with respect to each other such that they are not aligned along the longitudinal axis of the valve body / fluid displacement chamber, a single fluid connection is established from said fluid displacement chamber to a first chamber of the multiple chambers, and simultaneous venting of another chamber, i.e., a second chamber, occurs via the ports of the first sealing plate (and the vent port of such second chamber). Alternatively, a single fluid connection can be established from the fluid displacement chamber to said at least one interface when the valve body is in another position.When a separate fluid treatment module is attached to such at least one interface, a single fluid connection is thus also established to such separate fluid treatment module attached to such at least one interface. As used herein, the term "first sealing plate" is sometimes referred to herein as a "top sealing plate". Similarly, the term "second sealing plate" is sometimes referred to herein as a "bottom sealing plate".
[0036] In one embodiment, typically, the chambers in the plurality of chambers are arranged adjacent to each other. The independent chambers may be divided or subdivided. As a minimum requirement, each of the plurality of chambers has a fluid port at its bottom and optionally a vent port at its top. In some embodiments, a chamber may have two or more fluid ports at its bottom and no vent port at its top, one vent port or two or more vent ports. In one embodiment, each chamber has exactly one fluid port at its bottom and exactly one vent port at its top. In some embodiments, depending on their respective functions, the chambers of the plurality of chambers may have functional parts inside, such as a filter.
[0037] In one embodiment, the housing and valve body have a circular cross-section. Preferably, the chambers of the plurality of chambers are disposed adjacent one another and around a preferably centrally located fluid displacement chamber. Preferably, in such an embodiment, the chambers are disposed adjacent one another like adjacent segments of a circle or adjacent pieces of a circular pie.
[0038] In some embodiments, adjacent chambers may be fluidically connected to each other. As an example, adjacent chambers may be fluidically connected to each other, and each of the three chambers may have a fluid port at the bottom of each and a vent port at the top of each. The fluidic connection between adjacent chambers may be a respective opening in the wall between the adjacent chambers. As an example, the first chamber may contain a filter element that may help to enhance certain analytes, such as nucleic acids, from the lysed sample, and may contain a high salt concentration buffer. The lysed sample may be applied to the first chamber through the first fluidic port at the bottom. Liquid may be transferred in both directions several times over the filter, as excess liquid may be transferred to a second chamber adjacent to the first chamber through an opening in the wall between the two chambers. Such a second chamber serves as a post-filter liquid capture chamber. If the applied volume of the lysed liquid sample also exceeds the volume of the post-filter liquid capture chamber, liquid may be transferred into the third chamber again through a fluidic connection, such as an opening between the second and third chambers, and such a third chamber serves as an overflow chamber. A different liquid may be dispensed into the second chamber through its fluid port at the bottom. Such liquid dispensed through the bottom fluid port of the second chamber may, however, also be pulled through a filter in the first chamber, for example to wash or elute material bound to the filter, by adjusting the valve body relative to the fluid port of the first chamber and applying a negative pressure, thus drawing the liquid contained in the second chamber into the first chamber and through the filter. Thus, complex work flows may be allowed by combining dedicated adjacent chambers with different functions, or by combining a particular chamber together with an adjacent interface for mounting an external module, for example, as described in more detail below.
[0039] It should also be noted that such an embodiment could be realized by subdividing a single chamber into three adjacent compartments, each compartment having its own fluid port at the bottom and its own vent port at the top, with the three compartments fluidly connected to each other. Note, however, that in either case, each chamber or compartment would still be closed, other than the presence of the fluid ports, vent ports and fluid connections between the chambers or compartments.
[0040] As used herein, the term "liquid handling and processing tool" is used interchangeably and synonymously with the term "cartridge for analyzing biological samples." The cartridge or liquid handling and processing tool according to the present invention, as described herein, is a "ready to fill" cartridge, which can be easily operated and handled after it is filled with the appropriate and intended reagents and is provided with the appropriate and intended reagents.
[0041] In one embodiment, the ports of the first and second sealing plates are aligned with each other along the longitudinal axis of the valve body. Preferably, the longitudinal axis of the valve body is also the longitudinal axis of the fluid displacement chamber. Preferably, the fluid displacement chamber has a piston (sometimes referred to herein as a "plunger") movable within the fluid displacement chamber and capable of drawing liquid from the fluid displacement chamber and expelling liquid from the fluid displacement chamber. The fluid displacement chamber is centrally located within the valve body and aligned along the longitudinal axis of the valve body. Preferably, the valve body further includes a first circular sealing plate located at the top of the fluid displacement chamber and a second circular sealing plate located at the bottom of the fluid displacement chamber. The first and second circular sealing plates are fixedly connected to the valve body at the top and bottom of the fluid displacement chamber, respectively. The first circular sealing plate has a vent port located off-center of the first circular sealing plate and the second circular sealing plate has a fluid port located off-center of said second circular sealing plate. In one embodiment, at least one chamber of the plurality of chambers has a vent port at its apex, and preferably each of the plurality of chambers has a vent port at their respective apex.
[0042] As pointed out above, in said plurality of chambers, each chamber is closed, meaning that, except for the presence of a fluid port at the bottom of the respective chamber, and optionally a further port (a vent port) at the top, and further optionally an additional opening or loading port at the top, such chamber is closed and no substance, e.g. liquid, fluid or other chemical, can be added to or removed from such chamber. In one embodiment, the plurality of chambers is closed at the top by a single lid, and any vent port, if present, is located in the single lid.
[0043] In one embodiment, at least one chamber of said plurality of chambers further comprises a loading port for adding liquid to said chamber, such loading port being located at the top of said at least one chamber, said loading port, if present, being different from said vent port. It is noted that such loading port, if present, is preferably closable / sealable by a suitable cap, or plug, or lid, or seal. This allows adding a reagent or liquid or other substance to a particular chamber and then closing it again.
[0044] In one embodiment, some, and preferably all, of the multiple chambers each have a loading port for adding liquid or other substances to the respective chamber, the loading port being located at the top of the respective chamber, the loading port being distinct from any vent port, if present. In a preferred embodiment, the loading ports are located in a single lid that closes the multiple chambers at the top.
[0045] In one embodiment, the housing includes a number of interfaces for fluidly connecting individual fluid treatment modules to the housing, each of the number of interfaces including a single port.
[0046] In one embodiment, at least one chamber is a compartmentalized chamber having different compartments fluidly connected to each other, such compartments configured to perform different functions such as filtration, serving as a reservoir for processing fluids or serving as an overflow volume. In another embodiment, at least two chambers or possibly more chambers, for example three, four, five or more chambers, of said plurality of chambers are fluidly connected to each other, each of such at least two chambers configured to perform different functions such as filtration, serving as a reservoir for processing fluids or serving as an overflow volume, preferably said at least two chambers are fluidly connected to each other, each having a fluid port at the bottom and a vent port at the top. In one embodiment, one, some or all of such chambers also have a loading port at their respective tops.
[0047] As pointed out above, the channel in the sealing plate allows the valve body to establish a single fluid connection from the fluid displacement chamber to a selected one of the chambers or at least one interface, as mentioned above. Such a channel has no openings other than the opening of the fluid displacement chamber at the bottom and the port in the second sealing plate, but is otherwise a closed channel. The channel may be configured to be a tunnel in the second sealing plate, or may be a groove in the second sealing plate covered by an additional cover or lid on top of the groove.
[0048] In one embodiment, the at least one interface comprises a port for fluidly connecting an external module, e.g. an external fluid treatment module, to the housing, the single port being not part of any of the multiple chambers but configured to allow attachment of an external module, e.g. a fluid treatment module or other module, to the housing from outside. Thus, since such a single port is not located in any of the (closed) chambers, it can be accessed and reached from the outside, allowing such external attachment.
[0049] Sealing of the plurality of chambers by the first and second sealing plates is preferably achieved by employing a suitable sealing material disposed between the respective plates and the housing, and / or by lining the first and second sealing plates and / or the housing with such a suitable sealing material, and / or by configuring the first and second sealing plates and the housing such that the respective sealing plates are pressed against the housing with sufficient force to seal the plurality of chambers, preferably the suitable sealing material being selected from elastomeric, thermoplastic and other plastic materials.
[0050] It should be noted that the liquid handling and processing tools (i.e., cartridges) are made from suitable plastic materials and may be manufactured by any suitable manufacturing technique known to those skilled in the art, such as molding techniques, extrusion techniques, 3D printing techniques, and others, as well as combinations of the foregoing.
[0051] In one embodiment, the channel in the second sealing plate comprises: a) an optical setup capable of detecting the presence, volume and / or optical properties of any fluid in a channel; b) a pressure sensor for determining the pressure in said liquid handling and processing tool, preferably in said channel. The device is configured to be interrogated by either
[0052] In one embodiment, such an optical setup is a reflective optical setup, e.g. a light barrier, and / or the body pressure sensor is a piezo-based pressure sensor.
[0053] In one embodiment, the liquid handling and processing tool further comprises at least one fluid processing module attached to said at least one interface through said single port of said at least one interface, or to several such interfaces, if present, In the latter case, when at least one fluid processing module is attached to several such interfaces, such interfaces are typically located adjacent to each other.
[0054] In one embodiment, the fluid processing module attached to the at least one interface via the single port is a module configured to perform a nucleic acid amplification reaction, a module configured to enrich or purify an analyte of interest, e.g., a nucleic acid, or a module for disrupting, homogenizing, and / or lysing a biological sample. In one embodiment, the module for disrupting, homogenizing, and / or lysing a biological sample includes a chamber containing a grinding medium comprising beads or balls configured to be agitated from outside the module.
[0055] In one embodiment, when the fluid processing module is a module configured to concentrate or purify an analyte of interest, such a module is a chamber containing a suitable medium that has an affinity for the analyte of interest.
[0056] In one embodiment, when the fluid treatment module is a module configured to perform a nucleic acid amplification reaction, such a nucleic acid amplification module has an opening by which the nucleic acid amplification module is fluidly connected to a single port of said interface, preferably such opening is the only opening of such a fluid treatment module.
[0057] In one embodiment, the fluid treatment module includes a frame enclosing a volume having at least one wall that is flexible and conformable to an external temperature regulating surface.
[0058] In one embodiment, the fluid treatment module further includes a rigid wall region that is transparent or otherwise suitable for optical interrogation by an external optical sensor such that the fluid treatment module is configured to enable detection of contents within the fluid treatment module.
[0059] In one embodiment, the fluid treatment module includes a frame enclosing a volume having at least one wall that is flexible and conformable to an external temperature regulating surface. In one embodiment, the fluid treatment module further includes a rigid wall region that is transparent or otherwise suitable for optical interrogation by an external optical sensor such that the fluid treatment module is configured to enable detection of contents within the fluid treatment module. In one embodiment, when a frame encloses a volume having at least one wall that is flexible and conformable to an external temperature regulating surface and when the fluid treatment module further includes a rigid wall region that is transparent or otherwise suitable for optical interrogation, such flexible wall and such rigid wall region are located opposite one another.
[0060] In one embodiment, the fluid treatment module has a bisected volume consisting of a first part and a second part, the first part being a first volume directly connected to and in communication with the opening of the fluid treatment module, in which sample processing and optionally detection of a processing reaction takes place, and the second part being a second volume connected only to the first part via a connecting tube, but otherwise closed, for receiving the overflow of liquid or gas (i.e. fluid) from the first part and for acting as a pressure accumulator.
[0061] In one embodiment, the first volume is of two opposing walls, one of which is formed by said flexible wall or a part thereof, and the other of which is formed by said rigid wall region or a part thereof. It should be noted that in an embodiment, typically, said rigid wall region is not an integral part of said frame and is removable therefrom. In such an exemplary embodiment, the rigid wall region is a separate manufactured part from said frame and is a separate component that can be attached to said frame, for example by clipping, gluing or otherwise connecting it to said frame.
[0062] In one embodiment, at least one chamber of the plurality of chambers has an outer wall accessible from outside the housing, such outer wall being configured to be contacted by a temperature adjustment device (preferably not forming part of the liquid handling and processing tool but provided from the outside), thus enabling temperature control within said at least one chamber when the temperature adjustment device contacts such outer wall.
[0063] In a further aspect, the present invention also relates to a fluid treatment and detection module for treating a liquid sample and detecting an analyte in said sample, such fluid treatment and detection module being configured for use in conjunction with a liquid handling and processing tool as defined above, i.e. for use in conjunction with a cartridge as defined above. Such a fluid treatment and detection module is configured for attachment to said at least one interface of said liquid handling and processing tool via said single port of said at least one interface. The fluid treatment and detection module comprises: a frame enclosing the volume, the frame having at least one wall that is flexible and conformable to an external temperature regulating surface; a rigid wall region that is transparent or otherwise suitable for optical interrogation by an external optical sensor, the rigid wall region preferably being removable from, and not an integral part of, said frame; an opening by which the fluid handling and detection module is fluidly connectable to the single port of the interface of the liquid handling and processing tool, preferably the opening of the fluid handling and detection module being the only opening of the module; Includes.
[0064] It should be noted that such a "fluid processing and detection module for processing liquid samples and detecting analytes in said samples" is sometimes referred to herein as a "nucleic acid amplification module" since it is configured to perform a nucleic acid amplification reaction.
[0065] It should be noted that in embodiments, typically the rigid wall region is not an integral part of the frame and is removable therefrom, in such exemplary embodiments the rigid wall region is a separate manufactured part from the frame and is a separate component that can be attached to the frame, for example by clipping, gluing or otherwise connecting it to the frame.
[0066] In one embodiment, such a fluid processing and detection module comprises a bifurcated volume consisting of a first part and a second part, the first part being a first volume directly connected to and in communication with the opening of the fluid processing and detection module, in which sample processing and detection of any processing reactions, such as nucleic acid amplification reactions, take place, and the second part being a second volume connected only to the first part via a connecting tube, but which is otherwise a closed volume, the second part being a volume for receiving liquid or gas overflow from the first part and for acting as a pressure accumulator.
[0067] In one embodiment, the first volume has two opposing walls, one of which is formed by a flexible wall region as defined above or part thereof, and the other of which is formed by a rigid wall region as defined above or part thereof. [Brief description of the drawings]
[0068] The invention will now be further described with reference to the following figures, given by way of example to illustrate, but not to limit, the invention. [Figure 1] 1 shows an exploded view of an embodiment of a liquid handling and processing tool according to the present invention. [Diagram 2] 1 shows an exploded view of an embodiment of a liquid handling and processing tool according to the present invention. [Diagram 3] 1 shows an assembled liquid handling and processing tool. [Figure 4] It is shown how additional fluid treatment modules can be attached to the assembled liquid handling and treatment tool by simply connecting such external modules to the respective interfaces of the housing. [Diagram 5] 1 shows a liquid handling and processing tool with two external fluid processing modules attached to the assembled liquid handling and processing tool. [Figure 6] 1 shows an assembled liquid handling and processing tool with a modified housing lid with an additional opening (loading port). [Figure 7a] 5 and 6 show top views of an assembled liquid handling and processing tool with two external fluid processing modules attached. [Figure 7b] A cross section along line AA shown in FIG. 7a is shown. [Figure 8a] FIG. 4 shows a top view of the assembled liquid handling and processing tool of FIG. [Figure 8b] 8 shows a cross section taken along line BB shown in FIG. 8a. [Figure 9a] The design of the external module attached to the liquid handling and processing tool is shown in Figure 8. An exploded view of such an external fluid processing module attached to the housing via a single port is shown. [Figure 9b] In FIG. 8, a design of an external module mounted on a liquid handling and processing tool is shown. [Figure 10] 1 shows a cross-section of a three-dimensional view of a liquid handling and processing tool with an external fluid processing module attached. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0069] FIG. 1 shows an exploded view of an embodiment of a liquid handling and processing tool according to the invention, said tool comprising a housing with multiple chambers. The chambers may comprise fluid ports at their bottoms and vent ports at their tops. The chambers are formed by attaching a lid to the housing. The lid comprises an opening (= port or vent port) that is reversibly sealed by a first sealing plate. The first sealing plate has at least one port that can be contacted with any of the openings in the lid (= ports of the independent chambers) by rotating the valve body and thus the first sealing plate attached thereto. The valve body is centrally located in the housing. The valve body consists of a fluid displacement chamber with a plunger (or piston) similar to a syringe, and a second sealing plate comprises a fluid channel that connects the fluid displacement chamber with the port of the second sealing plate. The fluid channel is formed by attaching the lid to a groove in said second sealing plate (see also FIGS. 7b, 8b and 10). The first and second sealing plates are fixedly connected to the valve body.
[0070] When assembled, the valve body and the first and second sealing plates comprise a single mechanical component that facilitates sealing of the chambers in the housing and provides intentional fluid access to the respective chambers through the fluid ports in the second sealing plate and venting of the chambers through the ports in the first sealing plate.
[0071] The housing also features one or several interfaces for connecting external fluid treatment modules, each such interface including a single port.
[0072] FIG. 2 shows an exploded view of an embodiment of a liquid handling and processing tool according to the invention, said tool further comprising an additional opening (loading port) in the housing lid, which opening is not sealed by the first sealing plate. Such an opening may be useful for adding materials, e.g. samples to be processed, after the liquid handling and processing tool is assembled, and is therefore sometimes referred to herein as a "loading port". A separate cap is provided for sealing such an additional opening. A filter may be attached to the vent port in the first sealing plate to prevent any liquid or solid material from leaving the addressed chamber and to ensure venting of the respective chamber. The drawing exemplarily shows two external fluid processing modules that will be attached to the ports of the housing, allowing the attachment of such external modules. One fluid processing module is shown with one connector to a single port of the housing, while the other fluid processing module is connected to two separate ports of the connection housing.
[0073] FIG. 3 shows the assembled liquid handling and processing tool with one external module attached to it and covering an opening (loading port) in its housing lid.
[0074] FIG. 4 shows how additional fluid processing modules can be attached to the assembled liquid handling and processing tool by simply connecting such external modules to the respective interfaces of the housing, where there are corresponding ports required for such connections.
[0075] FIG. 5 shows a liquid handling and processing tool with two external fluid processing modules attached to the assembled liquid handling and processing tool.
[0076] FIG. 6 shows an assembled liquid handling and processing tool with a modified housing lid with an additional opening (loading port). Such an opening is useful for adding liquid or solid reagents to the liquid handling and processing tool after it has been mechanically assembled. To still provide a complete sealing of the chambers with the respective reagents, an additional seal is provided that is placed in the opening (loading port) on the outside of the first sealing plate. Such a seal can be attached to the housing by different means, for example by an adhesive layer, chemical or solvent bonding, laser or ultrasonic welding techniques.
[0077] Figure 7a shows a top view of the assembled liquid handling and processing tool of Figures 5 and 6 with the two external fluid processing modules attached. Figure 7b shows a cross section along the line AA indicated in Figure 7a. The left chamber is isolated and sealed, while the right chamber is fluidly connected to the fluid displacement chamber through a channel in the bottom of the second sealing plate. The right chamber also features an opening in its top lid (a vent port). This opening is aligned with and connected to a port in the first sealing plate, thus the chamber is vented.
[0078] Figure 8a shows a top view of the assembled liquid handling and processing tool of Figure 3 with one external fluid processing module installed and two ports available for mounting further external fluid processing modules. Figure 8b shows a cross section along line BB indicated in Figure 8a. On the left, the housing provides an open space to accommodate additional external modules, while on the right, an external module is shown mounted to the housing through a single port. The module is fluidly connected through a port in the second sealing plate but is not vented (there is no vent port on the top).
[0079] FIG. 9 shows the design of the external module attached to the liquid handling and processing tool in FIG. 8. FIG. 9a shows an exploded view of such an external fluid processing module attached to the housing via a single port. The illustrated module is configured to perform nucleic acid amplification reactions. The module comprises a frame, to which two walls are attached. The first wall is flexible and conformable to an external temperature regulating surface, the second wall is rigid and transparent to facilitate optical interrogation of (bio)chemical reactions within the chamber. The illustrated design comprises a bisected volume consisting of a first part and a second part, the first part being the first volume directly connected to and in communication with the ports of the fluid processing and detection module. In this first part, the processing of the sample and the detection of any processing reactions take place. The second part is a second volume connected only to the first part via a connecting tube, but otherwise represents a closed volume to receive the overflow of liquid or gas from the first part and to act as a pressure accumulator.
[0080] FIG. 10 shows a cross-section of a three-dimensional view of a liquid handling and processing tool with an external fluid processing module attached. [Explanation of symbols]
[0081] 1 Liquid handling and processing tools or cartridges 2 Valve body 21 Fluid displacement chamber having: 211 (of the fluid displacement chamber) top, and 212 (of the fluid displacement chamber) bottom, and 2111 the opening at the top, and 2121 Bottom opening 2112 First sealing plate at the top of the fluid displacement chamber (=top sealing plate / first circular sealing plate) 2121 Second sealing plate at the bottom of the fluid displacement chamber (= bottom sealing plate / second circular sealing plate) 21121 Port of the first sealing plate (=ventilation port located off-center of the first sealing plate) 21122 Opening in the first sealing plate 21211 Second sealing plate port (= fluid port located off-center of the second sealing plate) a channel in a second sealing plate extending radially from and terminating at the 21211 fluid port of the second sealing plate; 21213 Opening in the second sealing plate 21214 Channel Lid 213 Piston / plunger of said fluid displacement chamber 3 Housing having multiple of the following: 31, 31', 31'', 31''',... chambers for holding a reagent or receiving a liquid, each of said chambers having: 311 (of the chamber) top, and 312 (of the chamber) bottom 3121 Bottom fluid port (of each chamber) 3111 Top vent port (of chamber) 32 at least one interface for fluidly connecting an individual fluid treatment module to said housing; 321 (of said at least one interface) a single port 3112 A loading port (of at least one of the chambers) for adding liquid to the chamber, the loading port being located at the top of the at least one of the chambers. 313 a single lid closing the multiple chambers at the top 3111 Vent port in single lid 314, 314', 314'' compartments of a compartmented chamber fluidly connected to one another and configured to perform different functions 315 an outer wall of the chamber accessible from outside the housing 4. a fluid treatment module attached to said at least one interface or, if present, several such interfaces via said single port of said at least one interface; 41 an opening in a fluid treatment module, whereby the fluid treatment module is fluidly connected to the single port of the interface; 42 Frame of a fluid processing module enclosing: 421 Volume having at least 4211 One wall that is flexible and can be fitted with an external temperature regulating surface; 4212 Rigid wall area, transparent or otherwise suitable for optical interrogation by an external optical sensor
Claims
1. A liquid handling and processing tool (1) for analyzing biological samples, comprising: a) a valve body (2) including a fluid displacement chamber (21), said fluid displacement chamber having a top (211) and a bottom (212) and an opening (2111) at the top and an opening (2121) at the bottom, respectively, said fluid displacement chamber allowing for aspirating liquid therefrom and expelling liquid therefrom, said valve body further including a first sealing plate (2112) at the top and a second sealing plate (2121) at the bottom, said first sealing plate at the top and said opening (2122) at the bottom being sealed by a sealing member (2124) and a sealing member (2126) at the bottom. a valve body (2) wherein the second sealing plate is fixedly coupled to one another via the fluid displacement chamber, each of the first and second sealing plates having a port (21121, 21211), the fluid displacement chamber being fluidly connected to the port of the second sealing plate via a channel (21212) in the second sealing plate, the channel extending from the opening (2121) of the fluid displacement chamber at the bottom and terminating in the port (21211) of the second sealing plate; b) a housing (3) having a plurality of chambers (31, 31', 31'', 31''') for holding reagents or receiving liquids, each of said chambers having a top (311) and a bottom (312), respectively, a fluid port (3121) at said bottom, and optionally a vent port (3111) at said top, said housing further comprising at least one interface (32) for fluidly connecting a separate fluid processing module to said housing, said at least one interface comprising a single port (321); wherein said valve body and said housing are arranged in such a way that said fluid displacement chamber is located within said housing, said valve body is rotatable within said housing, said first sealing plate seals said plurality of chambers at their respective tops and said second sealing plate seals said plurality of chambers at their respective bottoms, and said valve body is configured to establish a single fluid connection from said fluid displacement chamber to a selected one of said plurality of chambers via said channel and via said port of said second sealing plate and optionally to allow simultaneous venting of the same or another chamber via said port of said first sealing plate, or said valve body is configured to establish a single fluid connection from said fluid displacement chamber to said at least one interface and to any individual fluid treatment module attached to said interface, if present, via said channel and via said port of said second sealing plate.
2. A liquid handling and processing tool (1) for analyzing biological samples, in particular a liquid handling and processing tool according to claim 1, a) a valve body (2) having a longitudinal axis and including a fluid displacement chamber (21) along said longitudinal axis, said fluid displacement chamber having a top (211) and a bottom (212) and an opening (2111) at said top and an opening (2121) at said bottom, respectively; the fluid displacement chamber further comprising a piston (213) movable within the fluid displacement chamber and enabling the drawing of liquid into the fluid displacement chamber and the expulsion of liquid from the fluid displacement chamber; the fluid displacement chamber is centrally located within the valve body and aligned along the longitudinal axis of the valve body; The valve body (2) further includes a first circular sealing plate (2112) located at the top of the fluid displacement chamber and a second circular sealing plate (2121) located at the bottom of the fluid displacement chamber; the first circular sealing plate (2112) is fixedly connected to the valve body at the top of the fluid displacement chamber and has a vent port (21121) located off-center of the first circular sealing plate, the first circular sealing plate allowing access to the opening (2111) of the fluid displacement chamber at the top by an opening (21122) in the first circular sealing plate that is aligned with the opening (2111) at the top of the fluid displacement chamber; the second circular sealing plate (2121) is fixedly connected to the valve body at the bottom of the fluid displacement chamber and has a fluid port (21211) located off-center of the second circular sealing plate, the second circular sealing plate allowing access to the opening (2121) of the fluid displacement chamber at the bottom by an opening (21213) in the second circular sealing plate that is aligned with the opening (2121) at the bottom of the fluid displacement chamber; the vent ports (21121) of the first circular sealing plate and the fluid ports (21211) of the second circular sealing plate are aligned with one another; the second circular sealing plate further comprising a channel (21212) extending radially from the opening (21213) in the second circular sealing plate and terminating in the fluid port (21211) located off-center of the second circular sealing plate, the valve body thus being configured to establish a single fluid connection with the off-center fluid port of the second circular sealing plate via the channel; b) a housing (3) comprising a plurality of chambers (31, 31', 31", 31'") for holding reagents or receiving liquids, said chambers being arranged around a central hollow space, each of said chambers having a top (311) and a bottom (312), respectively, a fluid port (3121) at said bottom, and optionally a vent port (3111) at said top, said housing further comprising at least one interface (32) for fluidly connecting a separate fluid treatment module to said housing, said at least one interface comprising a single port (321); wherein the valve body and the housing are arranged in such a manner that the fluid displacement chamber is located within the central hollow space, the valve body is rotatable within the central hollow space about the longitudinal axis, the first circular sealing plate of the valve body seals the plurality of chambers at their respective tops, the second circular sealing plate of the valve body seals the plurality of chambers at their respective bottoms, and the valve body provides fluid communication between the plurality of chambers and the fluid displacement chambers via the channels and via the fluid ports at the bottom of the second circular sealing plate.
2. A liquid handling and processing tool (1), in particular a liquid handling and processing tool as claimed in claim 1, wherein the valve body is configured to establish a single fluid connection from the fluid displacement chamber to the at least one interface and, if present, any individual fluid processing module attached to the interface, via the channel and via the fluid port in the bottom of the second circular sealing plate, and optionally to allow simultaneous venting of the same or another chamber via the vent port in the first circular sealing plate.
3. A liquid handling and processing tool as described in claim 2, wherein the opening (21122) in the first circular sealing plate is a central opening and the opening (21213) in the second circular sealing plate is a central opening.
4. The liquid handling and processing tool of any one of claims 1 to 3, wherein the ports of the first and second sealing plates are aligned with each other along a longitudinal axis of the valve body.
5. The liquid handling and processing tool of any one of claims 1 to 4, wherein at least one chamber of the plurality of chambers has a vent port (3111) at its top.
6. A liquid handling and processing tool as described in claim 5, wherein each of the plurality of chambers has a vent port at its respective top.
7. A liquid handling and processing tool as claimed in any one of claims 1 to 6, wherein the multiple chambers are closed at the top by a single lid (313) and any vent port (3111), if present, is located in the single lid (313).
8. 8. A liquid handling and processing tool as described in any one of claims 1 to 7, wherein at least one of the plurality of chambers further has a loading port (3112) for adding liquid to the chamber, the loading port being located at the top of the at least one chamber, and the loading port, if present, being different from the vent port.
9. 9. A liquid handling and processing tool as described in any one of claims 1 to 8, wherein some of the chambers of the plurality of chambers each have a loading port (3112) for adding liquid to the respective chamber, the loading port being located at the top of the respective chamber, and the loading port being distinct from any vent port, if present.
10. A liquid handling and processing tool as described in claim 9, wherein all of the chambers of the plurality of chambers each have a loading port (3112) for adding liquid to the respective chamber.
11. The liquid handling and processing tool according to any one of claims 8 to 10, wherein the loading ports are located in the single lid (313).
12. A liquid handling and processing tool as claimed in any one of claims 1 to 11, wherein the housing comprises a number of interfaces (32, 32', 32'') for fluidly connecting individual fluid processing modules to the housing, each of the number of interfaces comprising a single port (321, 321', 321''').
13. 13. The liquid handling and processing tool of any one of claims 1 to 12, wherein at least one chamber is a compartmentalized chamber having different compartments (314, 314', 314'') fluidly connected to each other and configured to perform different functions such as filtration, serving as a reservoir for processing a fluid or serving as an overflow volume, or at least two chambers of the plurality of chambers are fluidly connected to each other and each of the at least two chambers is configured to perform different functions such as filtration, serving as a reservoir for processing a fluid or serving as an overflow volume.
14. The liquid handling and processing tool of claim 13, wherein the at least two chambers are fluidly connected to each other and each have a fluid port at the bottom and a vent port at the top.
15. A liquid handling and processing tool as described in any one of claims 1 to 14, wherein the channel (21212) has no other openings other than the opening (2121) of the fluid displacement chamber at the bottom and the port (21211) of the second sealing plate, but is otherwise a closed channel.
16. A liquid handling and processing tool according to any one of claims 1 to 15, wherein the single port of the at least one interface for fluidly connecting a fluid processing module to the housing is not part of any of the multiple chambers and is configured to allow attachment of a fluid processing module or other module to the housing from outside.
17. 17. A liquid handling and processing tool according to any one of claims 1 to 16, wherein sealing of the plurality of chambers by the first and second sealing plates is achieved by using a suitable sealing material disposed between the respective plates and the housing, and / or by lining the first and second sealing plates and / or the housing with the suitable sealing material, and / or by configuring the first and second sealing plates and the housing such that the respective sealing plates are pressed against the housing with sufficient force to seal the plurality of chambers, preferably the suitable sealing material is selected from elastic, thermoplastic and other plastic materials.
18. The channel in the second sealing plate comprises: a) an optical setup capable of detecting the presence, volume and / or optical properties, e.g. visible color, fluorescence, extinction, of any fluid in said channel; b) a pressure sensor for determining the pressure in said liquid handling and processing tool, preferably in said channel.
18. A liquid handling and processing tool according to any one of claims 1 to 17, configured to be interrogated with either a liquid handling or processing tool, preferably wherein the optical set-up is a reflective optical set-up, such as a light barrier, and / or wherein the pressure sensor is a piezo based pressure sensor.
19. A liquid handling and processing tool according to any one of claims 1 to 18, further comprising at least one fluid processing module (4) attached to said at least one interface (32) or to several of said interfaces (32, 32', 32''), if present, via said single port (321) of said at least one interface.
20. A liquid handling and processing tool as described in claim 19, wherein the fluid processing module is a module configured to perform a nucleic acid amplification reaction, a module configured to concentrate or purify an analyte of interest, such as a nucleic acid, or a module for disrupting, homogenizing and / or lysing a biological sample.
21. A liquid handling and processing tool as described in claim 20, wherein the fluid processing module (4) is a module configured to perform a nucleic acid amplification reaction, and the nucleic acid amplification module has an opening (41) whereby the nucleic acid amplification module is fluidly connected to the single port (321) of the interface.
22. A liquid handling and processing tool as described in claim 21, wherein the opening (41) is the only opening in the fluid processing module.
23. A liquid handling and processing tool according to any one of claims 19 to 22, wherein the fluid processing module comprises a frame (42) enclosing a volume (421) having at least one wall (4211) that is flexible and conformable to an external temperature regulating surface.
24. 24. The liquid handling and processing tool of claim 23, wherein the fluid processing module further comprises a rigid wall region (4212) that is transparent or otherwise suitable for optical interrogation by an external optical sensor such that the fluid processing module is configured to enable detection of contents within the fluid processing module.
25. A liquid handling and processing tool as described in claim 24, wherein the rigid wall region is removable from the frame and is not an integral part thereof.
26. 25. A liquid handling and processing tool according to any one of claims 19 to 24, wherein the fluid processing module has a bisected volume consisting of a first part and a second part, the first part being a first volume directly connected to and in communication with the opening of the fluid processing module, in which sample processing and optionally detection of a processing reaction takes place, and the second part being a second volume connected only to the first part via a connecting tube but otherwise closed, the second volume being a volume for receiving liquid or gas overflow from the first part and acting as a pressure accumulator.
27. A liquid handling and processing tool as described in claim 26, wherein the first volume has two opposing walls, one of which is formed by a flexible wall (4211) as described in claim 23 or part thereof, and the other of which is formed by a rigid wall region (4212) as described in claim 24 or 25 or part thereof.
28. 28. A liquid handling and processing tool as claimed in any one of claims 1 to 27, wherein at least one chamber of the plurality of chambers has an outer wall (315) accessible from the exterior of the housing, the outer wall being configured to be contacted by a temperature adjustment device, thereby enabling temperature control within the at least one chamber when a temperature adjustment device contacts the outer wall.
29. A fluid treatment and detection module (4) for treating a liquid sample and detecting an analyte in said sample, said fluid treatment module being adapted for use in conjunction with a liquid handling and processing tool (1) according to any one of claims 1 to 18 and adapted to be attached to said at least one interface (32) of said liquid handling and processing tool via said single port (321) of said at least one interface, said fluid treatment module comprising: A frame (42) enclosing a volume (421) having at least one wall (4211) that is flexible and conformable to an external temperature regulating surface; a rigid wall region (4212) that is transparent or otherwise suitable for optical interrogation by an external optical sensor; an opening (41) by which the fluid processing and detection module is fluidly connectable to the single port (321) of the interface (32) of the liquid handling and processing tool; A fluid handling and detection module (4).
30. A liquid handling and processing tool as described in claim 29, wherein the rigid wall region is removable from the frame and is not an integral part of the frame.
31. 31. The liquid handling and processing tool of claim 29 or 30, wherein the opening in the fluid processing and detection module is the only opening in the module.
32. 32. A fluid processing and detection module according to any one of claims 29 to 31, comprising a bifurcated volume consisting of a first part and a second part, the first part being a first volume directly connected to and in communication with the opening of the fluid processing and detection module, in which processing of a sample and detection of any processing reaction takes place, and the second part being a second volume connected only to the first part via a connecting tube but otherwise closed, the second part being a volume for receiving liquid or gas overflow from the first part and for acting as a pressure accumulator.
33. A liquid handling and processing tool as described in claim 32, wherein the first volume has two opposing walls, one of which is formed by a flexible wall (4211) as described in claim 29 or part thereof, and the other of which is formed by a rigid wall region (4212) as described in claim 29 or 30 or part thereof.
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