Analytic device, liquid handling system and chemical analysis method

Abstract

An analytical device comprising a planar analytic region and a liquid handling system is proposed, wherein the liquid handling system includes an actor structure, a retaining structure, and a biasing structure, wherein the actor structure is configured to act upon a liquid barrier for a liquid when released by the retaining structure, wherein the biasing structure is configured to apply a mechanical force urging the actor structure towards the retaining structure, and wherein the retaining structure is configured to retain the actor structure when in a dry state, and to release the actor structure when in a wet state. A liquid handling system for an analytical device and a a method for performing a chemical analysis are also proposed.

Description

FIELD

[0001] The present disclosure relates to an analytic device, to a liquid handling system and to a chemical analysis method.BACKGROUND

[0002] Various analytical techniques require a targeted release, application or blockage of liquids at certain positions of an analytical device. Hereinbelow, specific reference is made to thin layer chromatography (TLC), a physicochemical separation technique used to investigate the composition of samples of various origins. However, use of the instrumentalities proposed herein is not limited to this specific technique but applicable to a wide variety of methods and devices.SUMMARY

[0003] According to the present disclosure, an analytic device, a liquid handling system and a chemical analysis method comprising the features of the independent claims is proposed. Embodiments as proposed herein are the subject matter of the dependent claims and of the description that follows hereinbelow.

[0004] An analytical device as proposed herein comprises a planar analytic region and a liquid handling system, wherein the liquid handling system includes an actor structure, a retaining structure, and a biasing structure, wherein the actor structure is configured to act upon a liquid barrier for a liquid when released by the retaining structure, wherein the biasing structure is configured to apply a mechanical force urging the actor structure towards the retaining structure, and wherein the retaining structure is configured to retain the actor structure when in a dry state, and to release the actor structure when in a wet state.

[0005] The device proposed herein is particularly advantageous for providing a targeted and selective liquid release, transport or blockage at a certain position defined by the elements of the device. The device may be advantageous for applying liquid from a reservoir. Other advantageous applications include bridging and thereby connecting different regions of a device for a liquid transport therebetween, as well as disconnecting said regions, i.e. to provide a valve function.

[0006] Liquids that can be used with the device as proposed herein may include, but are not limited to, elution liquids, washing liquids, mobile phase liquids forming or being part of a separation system, reaction liquids reacting with certain moieties of analyte molecules, detection liquids, and the like.

[0007] If reference is made hereinbelow to a wetting liquid, wetting of the retaining structure is not necessarily the only function of the wetting liquid, but a wetting liquid can, like any other liquid referred to above, contain further functional components such as solvents, analyte molecules, stains, reactants, and many more.

[0008] The terms "wet" and "dry" are used herein to indicate different moisture contents, wherein a "dry" matter may particularly be at an equilibrium with a surrounding atmosphere and a "wet" matter has a moisture content above, which is caused by applying a wetting liquid thereto. The terms "wet" and "moisture" do not necessarily relate to water but may include any other liquid as well.

[0009] Similarly to a wetting liquid, the functions of the retaining structure are not necessarily limited to retaining the actor structure. Rather, further functions as generally known for porous planar elements of an analytical device can be present.

[0010] A biasing element in the language used herein may include at least one elastic element such as a spring or an elastomer, or any combinations thereof. A biasing element may also comprise further structures besides an elastic element. The biasing element generally presses the actor structure against the retaining structure which may e.g. disintegrate, break, tear, soften, or dissolve when wetted to release the actor structure.

[0011] According to certain embodiments as proposed herein, the retaining structure comprises at least one of fibres whose cohesion is reduced in the wet state and a material dissolved in the wet state.

[0012] By selecting appropriate materials, the properties of the retaining structure may be selectively defined. The retaining structure may, in certain embodiments, be a strip of material made from fibres such as paper. The material dissolved may also be a glue with which the retaining structure is mounted to a different structure, or a glue interconnecting structural elements such as fibres and the like. A wet state, in the language used herein, is a state in which the retaining structure contains a certain amount or a wetting liquid such as water sufficient to reduce the structural integrity of the retaining structure or the adhesion force of a glue.

[0013] According to certain embodiments as proposed herein, a liquid guiding element arranged between a liquid source region and the retaining structure may be provided which is configured to guide the wetting liquid from the application region to the retaining structure such as to bring the retaining structure into the wet state.

[0014] This allows for the application of a wetting liquid at a position different from that of the retaining structure itself and particularly to pass such a wetting liquid from an application position to the retaining structure. This may be advantageous, for example, if the retaining structure is at a position difficult to access by a manual or automated wetting liquid applicator such as a manual or automated pipette. It also allows for a time lag between the application of the wetting liquid and the time when the retaining structure is wetted by this liquid, comparable to a fuse cord. Such a time lag can be configured by selecting a certain length or liquid transporting properties of the wetting structure.

[0015] The liquid guiding element can be provided in any form suitable or arranged for guiding liquid, particularly using capillary forces. That is, the wetting structure can be, or include, fibrous structures, such as in paper, and can also include one or more capillaries made from a suitable material.

[0016] A liquid source region can, in embodiments as proposed herein, include a liquid application zone at which a user or an automated system, for example, can apply liquid, e.g. using a pipette, and which is configured for receiving a certain amount of liquid. This can, in certain embodiments, be a well or groove or a region in which a spongy liquid storage element is provided, or, in other embodiments, a liquid vessel with an opening for liquid release.

[0017] According to certain embodiments as proposed herein, the liquid barrier may be a structure contributing in enclosing a liquid reservoir. In particular, the structure contributing in enclosing the liquid reservoir includes a metallic material.

[0018] In such embodiments, well-proven and advantageous liquid reservoirs may be used, wherein a structure contributing in enclosing a liquid reservoir may be a wall, a lid, a region with certain wall properties and the like, of the liquid reservoir. In certain embodiments, a reservoir in the form of a blister unit may be used, such as known for tablet packings, wherein the lid is a metallic lid, particularly made from, or including, aluminium. A metallic lid may be advantageous in that it does not block a liquid passage by contracting when e.g. pierced by a piercing element as it does not provide a tight sealing around the piercing element, and may even be caused to tear to provide a larger liquid release opening.

[0019] According to certain embodiments as proposed herein, the actor structure comprises a piercing element configured to be retained by the retaining element when the retaining element is in the dry state and to pierce the retaining element and the cover of the structure contributing in enclosing the liquid reservoir when the retaining element is in the wet state to release a liquid from the liquid reservoir.

[0020] A piercing structure contributing in enclosing the liquid reservoir at only one position with one piercing element allows for a very targeted liquid release at a confined position. However, embodiments as proposed herein are not limited to one piercing element. Rather, arrays of piercing elements may be provided in order to increase the speed of the liquid release or obtain a more even distribution. To allow or improve a liquid release from the liquid reservoir, certain means may be provided which allow an ingress of air or another gas to compensate for the liquid drained from the liquid reservoir.

[0021] In certain embodiments, therefore, the device comprises a venting element configured to be retained by the retaining element when the retaining element is in the dry state and to act upon the cover of the structure contributing in enclosing the liquid reservoir when the retaining element is in the wet state to allow ingress of a gas, such as air, into the liquid reservoir.

[0022] A venting element may, for example, be or include a hollow needle which, like the piercing element, may pierce the structure contributing in enclosing the liquid reservoir, but is configured to allow an air ingress into the reservoir. The venting element generally may be operated like a piercing element referred to above.

[0023] According to certain embodiments as proposed herein, the retaining element and the structure contributing in enclosing the liquid reservoir are provided in a coplanar arrangement.

[0024] A coplanar arrangement is particularly advantageous when the retaining structure has further functions and passes on the liquid released from the reservoir. Liquid is released in such an arrangement to the retaining structure at a particularly well defined position.

[0025] In a specific configuration of embodiments described herein, the retaining element may be a sheet or strip of material, such as paper, which cannot be pierced by the piercing element in the dry state, but is able to be pierced in the wet state. Mechanical properties of the retaining element and a biasing force of a biasing element may be selected to allow for such a functionality.

[0026] According to certain embodiments as proposed herein, however, the liquid barrier may be provided as a flow barrier between planar regions selected from a gap and a material barrier between the planar regions of the device.

[0027] In such embodiments, a valve may be defined which includes a barrier which may be bridged by bridging elements, and which may be opened or closed by the interaction of the elements of the device proposed herein.

[0028] According to certain embodiments as proposed herein, therefore, a bridging element configured to bridge the planar regions in a bridging position is provided, wherein the actor structure is configured to move the bridging element to or from the bridging position when released by the retaining structure.

[0029] Embodiments as proposed herein may therefore be configured to open or close a valve defined by the planar regions and the bridging elements to either allow a liquid to passed on or to be blocked by the valve.

[0030] According to certain embodiments as proposed herein, the retaining element is provided as a tearing element configured to tear when in the wet state, such as to release the actor structure.

[0031] Use of a tearing element may be advantageous as an actor element may then act upon a bridging element using a larger actor surface which is not limited to the tip of a piercing element. As explained for a liquid guiding element above, also a tearing element, e.g. in the form of a paper strip, may allow for the application of a wetting liquid at a position different from that of the actor structure and particularly to pass such a wetting liquid onwards as needed. This may be advantageous, as explained for the liquid guiding element, if the actor structure is at a position difficult to access by a manual or automated wetting liquid applicator such as a manual or automated pipette, and it also allows for a time lag between the application of the wetting liquid and the time when the retaining structure is wetted by this liquid. Again, such a time lag can be configured by selecting a certain length or liquid transporting properties of the wetting structure.

[0032] According to certain embodiments as proposed herein, however, the actor element may also comprise a piercing element, the retaining structure being configured to be pierced by the piercing element, and the piercing element being configured to move the bridging element to or from the bridging position when piercing the retaining structure.

[0033] Such a configuration may particularly be used when space is limited as a piercing element may require less space than a different actor element.

[0034] According to certain embodiments as proposed herein, the bridging element may be configured to bridge a further flow barrier between further planar regions of the device in a further bridging position.

[0035] That is, a valve may be provided which in one position may bridge a first flow barrier and in a second position may bridge a second flow barrier.

[0036] According to certain embodiments as proposed, the analytic region comprises a porous layer including at least one of a fibrous material and porous particles.

[0037] Such embodiments may particularly be provided as devices partly or completely corresponding to thin layer chromatography devices.

[0038] The liquid handling system for an analytical device proposed herein includes an actor structure, a retaining structure, and a biasing structure, wherein the actor structure is configured to act upon a liquid barrier for a liquid when released by the retaining structure, wherein the biasing structure is configured to apply a mechanical force urging the actor structure towards the retaining structure, and wherein the retaining structure is configured to retain the actor structure when in a dry state, and to release the actor structure when in a wet state.

[0039] The method for performing a chemical analysis as proposed herein comprises providing a device as explained above in different embodiments, and wetting the retaining structure whereby the retaining structure releases the actor structure.

[0040] As to further details and advantages of the liquid handling system and the method proposed herein, reference is made to the explanations above in regarding the method proposed herein and its embodiments. Particularly, such a liquid handling system method may, in embodiments as proposed herein, be used in any of the embodiments as discussed herein.FIGURES

[0041] Embodiments as disclosed herein will now be described, by way of example only, with reference to accompanying drawings, in which Figures 1A to 1C schematically illustrate a liquid handling system according to an embodiment in three states of operation; Figures 2A and 2B schematically illustrate a partial view of a liquid handling system according to an embodiment in two states of operation; Figures 3A and 3B schematically illustrates a liquid handling system according to a further embodiment in two views; Figures 4A and 4B schematically illustrate a partial view of a liquid handling system according to an embodiment in two states of operation; Figure 5 schematically illustrates a partial view of a liquid handling system according to a further embodiment; Figures 6A to 6D schematically illustrate a side view of an analytical device according to a certain embodiment; and Figures 7A to 7D schematically illustrate a top view of an analytical device according to the embodiment shown in Figures 6A to 6D. EMBODIMENTS

[0042] In the Figures, elements of identical, essentially identical, functionally comparable, or technically compatible function and / or purpose may be identified with identical reference numerals, and repeated explanations may be omitted for reasons of conciseness. Explanations herein relating to devices, apparatus, arrangements, systems, etc. according to certain embodiments disclosed herein likewise may apply to methods, processes, procedures, etc. according to corresponding embodiments.

[0043] The various embodiments described herein are presented only to assist in understanding and teaching the claimed features. These embodiments are provided as a representative sample of embodiments only, and are not exhaustive and / or exclusive. It is to be understood that advantages, embodiments, examples, functions, features, structures, and / or other aspects described herein are not to be considered limitations on the scope of the invention as defined by the claims or limitations on equivalents to the claims, and that other embodiments may be utilised and modifications may be made without departing from the scope of the invention.

[0044] Various embodiments as disclosed herein may suitably comprise, consist of, or consist essentially of, appropriate combinations of the disclosed elements, components, features, parts, steps, means, etc., other than those specifically described herein. In addition, this disclosure may include other inventions not presently claimed, but which may be claimed in future, particularly when encompassed by the scope of the independent claims.

[0045] Before turning to embodiments as proposed herein, some features of thin layer chromatography methods, in which certain embodiments as proposed herein may be used, will be further discussed.

[0046] Thin layer chromatography is a physicochemical separation method used to investigate the composition of samples of various origins. For example, thin layer chromatography methods are used for routine substance purity or confirmation tests for pharmaceutical drugs, but also as research tools in biology, chemistry and medicine. Particular advantages of thin layer chromatography are low equipment requirements, speed, high separation efficiency and low substance usage.

[0047] In thin layer chromatography, a thin layer of small particles (e.g. silica gel, diatomaceous earth, aluminium oxide or cellulose) is typically used as the stationary phase. The stationary phase is uniformly applied to a carrier film or plate produced from materials such as plastic, aluminium or glass. Thin layer chromatography plates are commercially available in different layer thicknesses. Silica gel is usually used as the stationary phase in normal phase thin layer chromatography and serves as a polar adsorbent for the analyte molecules due to the free terminal hydroxyl groups. Silica gel or other materials may also be modified, e.g. by hydrophobic groups, or mixed with other materials, such as ion exchange resins, to provide different separation characteristics, e.g. as in reverse-phase thin layer chromatography or ion exchange thin layer chromatography.

[0048] Samples for thin layer chromatography often require extensive sample preparation, e.g. to enrich or concentrate components to be analysed or to remove unwanted components (so-called matrix). Furthermore, it is generally desired to perform analyte detection directly on the chromatographic plate, in order to reduce the processing effort by e.g. scraping off, extracting and externally analysing chromatographic spots.

[0049] In thin layer chromatography, but also in other methods for analysing samples, a liquid application at certain positions of an analytical device, such as on a thin layer chromatography plate, and in a reproducible manner may be required, for example to apply a mobile phase or eluent, a detection liquid or the like. Manual application, such as by using a pipette, may be error prone and unreliable.

[0050] Embodiments as proposed herein have been developed with the particular goal of providing a mechanism for automating the functioning of tests including, but not limited to, thin layer chromatography which require less hands-on time needed by an end user and which are very simple to use, ideally only requiring adding a sample onto the test and perform all other steps are automatic, and therefore, as mentioned, to reduce the possibility of human error.

[0051] Embodiments proposed herein may be used, for example, in connection with lateral flow assays, paper-based microfluidics, particle-based microfluidics or virtually all analytic methods and devices in which a porous material is used which may be required to be supplied with a certain liquid.

[0052] In a specific embodiment, a device as proposed includes a piece of paper which is attached to a holding structure and which is holding back an actor element biased by a spring as a biasing element. When the paper wets, it gets weaker and it cannot hold back the force of the spring anymore. This causes, in embodiments, the paper to be pierced by a piercing element or to be teared, thus enabling the actor structure to act upon a fluid barrier. Such embodiments can therefore be used to release liquid from reservoirs or move valves.

[0053] Particularly, embodiments as proposed herein may include blisters as liquid reservoirs which are generally known in the field of microfluidics, and which include a plastic receptacle and an aluminium lid. A piercing element may be configured to pierce the lid and thereby release the liquid.

[0054] As to the term "valve" used herein, reference is made to Figures 5A to 7D of international patent application PCT / EP2023 / 085913 and the corresponding explanations, which are incorporated herein by reference as far as legally admissible.

[0055] As shown in PCT / EP2023 / 085913 in Figures 5 and 6A to 5C, a solid phase extraction region can be provided in a first plane, a solid phase extraction material can be printed or otherwise placed in further region within a frame of a base silica material in a sufficient thickness and with only a slight or no overlap with the frame of the base silica material, and auxiliary regions in the form of two eluent application regions and an eluent sink region may also be provided, as well as a sample or analyte separation region as a further analytic region. Bridging regions may be provided in a second and a third plane. At least the solid phase extraction region or, more precisely, the base material frame, and the two mobile phase application regions are provided as disjoint thin layer regions separated by, e.g., unprinted spaces of a substrate, i.e. strips void of porous material forming diffusion barriers or, in the language as used herein, liquid barriers.

[0056] As further explained in connection with Figures 6A to 6E of PCT / EP2023 / 085913, the arrangement of the regions shown in Figure 5 in different layers allows for performing different steps of a solid phase extraction and subsequent chromatographic separation, and each of Figures 6A to 6E illustrates a corresponding step. For further details, reference is made to the description.

[0057] Figures 7A and 7B of PCT / EP2023 / 085913 illustrate how certain regions may be selectively bridged by using a bridging structure or region, referred to as bridging element herein, which is brought into contact with exactly two regions separated by a liquid barrier. The bridging elements, which may be silica gel layers attached to a substrate, may selectively be lowered and lifted in the same device. Further details are described in connection with Figures 7C and 7D of PCT / EP2023 / 085913.

[0058] In embodiments disclosed herein, different materials can be used for each of the structures passing liquid, such as silica particles screen printed to a substrate, as mentioned in PCT / EP2023 / 085913, and paper parts.

[0059] Figures 1A to 1C illustrate a liquid handling system 100 provided according to an embodiment proposed herein in three states of operation.

[0060] Liquid handling system comprises a body 101 including a cut-out 102 and a back plate 103. In the cut-out 102, a biasing element is provided in the form of a spring 104. A pressing plate 107 to which a piercing element 108 is attached is provided as an actor element. The piercing element 108 is retained using a retaining element 109 in the form of a paper strip. A cover element 110 is also provided and cover element 110 comprises certain cut-outs to holds a blister 111 in place, said blister 111 including a liquid reservoir 112 and a lid, e.g. made from aluminium, as a liquid barrier 113. The blister 111 contains a liquid which is illustrated by a raster hatch.

[0061] Figure 1A shows a configuration wherein the retaining element 109 is in the dry state and retains the actor element including the pressing plate 107 and the piercing element 108 such that the piercing element 108 cannot pierce the liquid barrier 113 in this state.

[0062] Figure 1B shows the application of a wetting liquid in the form of a white vertical arrow. The wetting liquid may, in all configurations as discussed herein, further components such as analyte molecules. As illustrated by horizontal arrows, the retaining structure 109, which is appropriately configured, distributes the wetting liquid sideways and partly in the direction to the piercing element 108.

[0063] Figure 1C shows a state wherein the wetting liquid has reached the piercing element 108 such that the retaining element 109 is no more able to retain the piercing element 108 and the piercing element 108 pierces the retaining element 109. The piercing element also pierces the liquid barrier 113 and therefore the liquid contained in the reservoir 112 drains therefrom, as illustrated by a vertical arrow, and is distributed horizontally in the retaining element 109.

[0064] Particularly important factors for the embodiment shown in Figures 1A to 1C include strength of the retaining structure 109, particularly a paper, in dry and wet states, sharpness, dimensions, shape and number of piercing element(s) 108, and a strength or biasing force of the biasing element 104. These parameters are particularly selected such as to work together, so that the piercing element 108 does not pierce the retaining structure 109 (and lid 113) when the retaining structure 109 is dry but will pierce it when the retaining structure 109 is wet.

[0065] The retaining structure 109 that is being pushed on by the piercing element 108 must be held tightly so that the piercing element 108 cannot push the retaining structure 109 up while the retaining structure 109 is in the dry state (i.e. the tension that holds the retaining structure 109 is actually holding piercing element 108 back). This feature may, even if not specifically indicated, a feature of all embodiments disclosed herein. The retaining structure 109 is particularly held in contact with the lid 113 of the reservoir or blister 111 already when the device 100 is assembled, to avoid that there is a small gap between the retaining structure 109 and the lid 113. The piercing element 108 is already somewhat pushing on the lid 113 also which helps the retaining structure 109 to hold the tension.

[0066] If a blister 111 is used, it may be advantageous to use a lid 113 from aluminium at the bottom of the blister 111, as the piercing element 108 must break this material. If a plastic material would be used, the piercing element 108 could push therethrough, but the plastic may be so tightly around the piercing element 108 that the liquid is still sealed in the reservoir. When the piercing element 108 pierces the blister 111, there must be possibility for air to get into the reservoir. Otherwise as the liquid runs out of the reservoir, low pressure forms above the liquid leading to slowing or stopping of flow. For example, an additional hollow needle may be provided alongside the piercing element. Alternatively, the piercing element 108 may be dimensioned such that the lid 113 rips up widely enough such that air may enter. When breaking, the material of the retaining structure 109 may be forced inside the blister 111 which may help to ensure that the latter is emptied more completely. As mentioned above, venting elements may also be provided.

[0067] Figures 2A and 2B schematically illustrate a partial view of a liquid handling system 200 according to an embodiment in two states of operation.

[0068] In the system 200, the liquid barrier, which is indicated with reference numeral 213, is a flow barrier between planar regions 214 and is, in this configuration, a gap therebetween. However, also a material barrier between the planar regions 214 can be provided in other configurations, e.g. produced from a hydrophobic material. As illustrated by cross-hatches, the planar regions 214 are arranged on a base 216, such as a glass plate. They can be formed of a porous material, e.g. a fibrous or particular material. A bridging element 215 is provided which likewise includes, as shown with cross-hatches, a porous layer.

[0069] Figures 2A and 2B show, in comparison, how a piercing element 108 may, in a dry state of a retaining element 109, as shown in Figure 2A, not pierce the retaining structure 109 but pierces the retaining structure 109 in a wet state illustrated in Figure 2B. This causes the actor structure which the piercing element 108 is part of to move the bridging element 215 in a bridging position in which it bridges the regions 214. Fluid can therefore pass the fluid barrier 213, as shown with a dashed arrow.

[0070] Figures 3A and 3B schematically illustrate a liquid handling system 300 according to a further embodiment in two views, i.e. a side view in Figure 3A and a partial top view in Figure 3B.

[0071] The liquid handling system 300 essentially corresponds to the liquid handling system 100 shown in Figure 1, but further includes a liquid guiding element 301, e.g. in the form of a paper strip, which is arranged between a liquid source region 302 and the retaining structure 109 and configured to guide the wetting liquid from the source region 302 to the retaining structure 109 such as to bring the retaining structure 109 into the wet state. A liquid flow in the liquid guiding element 301 is illustrated in Figure 3B in the form of a horizontal arrow.

[0072] Compared to embodiments without a liquid guiding element 301, a particularly advantageous aspect of such an approach is that it allows a smoother, more uniform, and faster movement of the piercing element 108. The reason for this is that, if in other embodiments such as in system 100, the retaining structure 109 is wetting, the material thereof, such as paper, starts expanding somewhat slowly already and gives way to the tension holding the piercing element 108 back. Therefore, there may be some slight movement already releasing some tension in the spring 104 before the liquid actually reaches the spot where the piercing element 108 is in contact with retaining structure 109. This is especially advantageously in case of "valves" as described herein as well because the small movement before the actual trigger may "direct" or correct the piercing element 108 to a certain extent which is therefore not aimed quite straight up but is at an angle. A greater variety of materials that start wetting from the reservoir can be used because the material of the liquid guiding element 301 can be optimized for liquid transfer and must not be selected to be stable enough to retain the piercing element 108.

[0073] Figures 4A and 4B schematically illustrate a partial view of a liquid handling system 400 according to an embodiment in two states of operation.

[0074] Different from liquid handling systems 100, 200 and 300, the retaining element 401 is provided in system 400 as a tearing element configured to tear when in the wet state, such as to release the actor structure. A dry state of retaining element 401 is illustrated in Figure 4A while a wet state, with the retaining element 401 having teared, is shown in Figure 4B. Furthermore, a bridging element 215 is provided which is configured to bridge a further flow barrier 413 between further planar regions 414 of the device in a further bridging position, as shown in Figure 4A, with a flow between planar regions 414, as shown with a dashed arrow in Figure 4A. The bridging element 215 is moved from this bridging position, thus separating planar regions 414, to another bridging position, as shown in Figure 4B.

[0075] Figure 5 schematically illustrates a partial view 500 of a liquid handling system according to a further embodiment. As illustrated in Figure 5, a retaining element 401 provided as a tearing element can also be provided in combination with a piercing element 108. Further functions are evident from a combination view of Figures 1A to 1C in combination with Figures 4A and 4B.

[0076] In the configurations wherein the retaining element 401 is provided as a tearing element, i.e. in systems 400 and 500, after the tearing element tears, the rest of the tearing element must be allowed to freely move so that the actor structure can move up without the tearing element getting in the way. To allow such a free movement, sufficient space may be provided on all sides of bridging element 215, such that the teared tearing element 401 does not block the upward movement.

[0077] Further aspects may be important as well, such as the angle in which the tearing element is provided. It is expected that holders may be required hold the paper in a way that allows to compensate the force of the biasing element in the opposite direction and there is a predetermined area for tearing the paper. It should always tear from the same place.

[0078] Since a piercing element is not used in these configurations, a sharpness of a piercing element is not an important factor here, but the strength of the biasing element and the tearing element (wet and dry) are important. An easy configuration factor is the width of the tearing element. By simply making the tearing element narrower, the mechanism will be triggered more easily.

[0079] In case of reservoir release, triggering of the release can be done even after a structure such as a paper at the bottom of the reservoir is wetted (i.e. another paper is at the bottom of the reservoir and not in contact with the retaining structure 109). This allows some more complex designs of tests, where some wetting or other process can be already happening on the paper (at the bottom of the reservoir) or this paper is totally dry and nothing is happening there yet.

[0080] In all configurations, complex actions can be achieved on a test automatically by using one or several valves and / or automatic reservoir release systems.

[0081] Even if, in the description above, a focus has been placed on liquid handling systems 100, 200, 300, 400 and 500, embodiments as disclosed herein may pertain to analytical systems including such liquid handling systems 100, 200, 300, 400 and 500, an example of which will be described hereinbelow.

[0082] Figures 6A to 6D show a device 1 in a state as provided (Figure 6A) and three different stages of an analysis (Figures 6B to 6D) in side views, and Figures 7A to 7D show the same device 1 in top views. Device 1 comprises subunits 1000, 2000 and 3000. Elements essentially described above indicated with reference numerals incremented by the reference number of the respective subunit. The indication by the individual reference numerals, and the grouping into subunits 1000, 2000, 3000 does not represent a limitation, however and is merely given for reference purposes.

[0083] Liquid reservoir 1111 is referred to as a "second" reservoir, and liquid reservoir 2111 is referred to as a "first" reservoir hereinbelow. A sample application area is indicated with 3001. Retaining element 2113 is also configured to distribute liquid, as is a structure 3003. Retaining element 2113 and structure 3003 may be provided as paper sheets or strips. A bridging element 3215 may include an arrangement 3004 comprising an, e.g., screen printed solid phase exchange material on a substrate such as glass, and therefore the arrangement 3004 may be referred to as a solid phase extraction arrangement. A liquid guiding element 2001 connects retaining element 2113 and the tearing element which is provided as the retaining element 1401.

[0084] If, as shown in Figure 6B with a white vertical arrow, a sample is applied to sample application area 3001, it accumulates in sample application area 3001 and is distributed sideways, as indicated with small horizontal arrows, and therefore towards the first reservoir 2111 and the solid phase extraction arrangement 3004.

[0085] This, as shown in Figure 6C, causes piercing of the first reservoir 2111 by piercing element 2108 as the material of the retaining element 2113 weakens. Liquid from first reservoir therefore is released and washes all sample towards solid phase extraction arrangement 3004, as indicated by a horizontal white arrow. The sample passes through the solid phase extraction arrangement 3004 wherein analyte molecules accumulate, and a liquid passes on to structure 3003, as shown with smaller black arrows. Simultaneously, and likewise indicated by a smaller black arrow, liquid is transported via liquid guiding element 2001 towards retaining structure 1401.

[0086] This causes tearing elements 1401 and 3401 to tear, as shown in Figure 6D. This causes second reservoir 1111 to be pierced and solid phase extraction arrangement 3004 to be moved upwards, disconnecting structures 2113 and 3003. Therefore, the liquid may elute from second reservoir 1111 which in turn allows the liquid to elute analyte molecules from solid phase extraction arrangement 3004 to, e.g. an analyte detection zone in which the analyte may form a coloured complex for detection.

[0087] Particularly the latter aspects are visible from the top views of Figures 7A to 7D for which the same explanations apply and in which corresponding elements are indicated with like reference numerals as before. Certain elements shown in the side views of Figures 6A to 6D are hidden beneath certain elements shown in the top views of Figures 7A to 7D.

[0088] As above, Figure 7B shows the distribution of the sample applied in the sample application region by horizontal arrows. Figure 7C shows how liquid from first reservoir 2111 is distributed and Figure 7D shows how the analyte from solid phase extraction arrangement 3004 is passed to an analyte detection zone which is indicated with 4000 in Figures 7A to 7D.

[0089] Device 1 may be used, for example, to transform an existing multi-step chemical analysis method for porphobilinogen (PBG) to an automated analysis. The currently used PBG testing kits consist of multiple steps that must be performed by a trained professional to complete the analysis. This makes the tests expensive and limits their use (e.g. during the night shift). However, with the liquid-handling system and particularly the device 1 as proposed herein, all the intermediate steps could be automated (save for sample addition and signal readout).

[0090] Urine may be used as the sample which is added to the sample application area 3001, and PBG may be retained in the solid phase extraction arrangement 3004 if the device 1 is operated as indicated above using water in first reservoir 2111. An acidic eluent contained in, and released from, second reservoir 1111 can be 1 M acetic acid, as used in conventional test kits. Other demonstrated options have been 0.5 M formic acid.

[0091] The acidic eluent frees the PBG from the solid phase extraction region 3004, and PBG is eluted to the detection zone 4000 where e.g. Ehrlich reagent is located. The Ehrlich reagent reacts with the PBG to form a coloured compound. The amount of PBG in the sample can be then quantified by the intensity of the coloured product visually or using technical means.

[0092] The usage of Ehrlich reagent on a paper-based devices has been successfully demonstrated before to analyse the content of indole in shrimps, as e.g. described in an article by S. Seetasang and T. Kaneta, "Dip-and-Read, Organic Solvent-Compatible, Paper-Based Analytical Devices Equipped with Chromatographic Separation for Indole Analysis in Shrimp", ACS Sens. 2022, 7, 4, 1194-1200.

[0093] In certain embodiments, liquid handling systems as proposed herein may be combined with existing lateral flow assay (LFA) assays.

[0094] Such combinations may be particularly useful when, in addition to a sample, any other liquid (buffer, reagent, diluent) is needed to be added to the test. Otherwise, this liquid needs to be added manually, and since the adding time or amount is often important it can increase the risk of error. Moreover, any additional steps performed by the end user increase the risk of error.

[0095] In general, this would be suitable for all kinds of LFA tests where this extra liquid addition step is needed. The feasibility of the approach has been tested with a commercial vitamin D test, such as the "Rapid Self-Test for the semi-quantitative detection of Vitamin D in Human Whole Blood" offered by PRIMA Lab SA, Balerna, Switzerland.

[0096] A liquid handling system 100 with a liquid reservoir similar as in Figure 1 was integrated before the sample addition area (since both of their work principle is based on capillary action, the materials wetting in either case had to be simply physically connected) and the reservoir was previously filled with the diluent liquid, provided in the test package. After adding a sufficient amount of sample, the actor structure acted on the liquid barrier of the reservoir and the diluent solution was released allowing to complete the analysis with the test.

Claims

1. An analytical device comprising: a planar analytic region; and a liquid handling system, wherein the liquid handling system includes an actor structure, a retaining structure, and a biasing structure, wherein the actor structure is configured to act upon a liquid barrier for a liquid when released by the retaining structure, wherein the biasing structure is configured to apply a mechanical force urging the actor structure towards the retaining structure, and wherein the retaining structure is configured to retain the actor structure when in a dry state, and to release the actor structure when in a wet state.

2. The device according to claim 1, wherein the retaining structure comprises at least one of fibres whose cohesion is reduced in the wet state and a material dissolved in the wet state.

3. The device according to claim 1 or 2, wherein a liquid guiding element is provided which is arranged between a liquid source region and the retaining structure and which is configured to guide the wetting liquid from the liquid source region to the retaining structure such as to bring the retaining structure into the wet state.

4. The device according to any one of the preceding claims, wherein the liquid barrier is a structure contributing in enclosing a liquid reservoir.

5. The device according to claim 4, wherein the structure contributing in enclosing the liquid reservoir includes a metallic material.

6. The device according to claim 4 or 5, wherein the actor structure comprises a piercing element configured to be retained by the retaining element when the retaining element is in the dry state and to pierce the retaining element and the structure contributing in enclosing the liquid reservoir when the retaining element is in the wet state to release a liquid from the liquid reservoir.

7. The device according to any one of the preceding claims, wherein the device comprises a venting element configured to act upon the structure contributing in enclosing the liquid reservoir when the actor structure acts upon the liquid barrier, to allow ingress of a gas into the liquid reservoir.

8. The device according to any one of claims 1 to 3, wherein the liquid barrier is a flow barrier between planar regions selected from a gap and a material barrier between the planar regions of the device.

9. The device according to claim 8, comprising a bridging element configured to bridge the planar regions in a bridging position, wherein the actor structure is configured to move the bridging element to or from the bridging position when released by the retaining structure.

10. The device according to any one of the preceding claims, wherein the retaining element is provided as a tearing element configured to tear when in the wet state, such as to release the actor structure.

11. The device according to any one of the preceding claims, wherein the actor structure comprises a piercing element, the retaining structure being configured to be pierced by the piercing element, and the piercing element being configured to move the bridging element to or from the bridging position when piercing the retaining structure.

12. The device according to any one of claims 9 to 11, wherein the bridging element is configured to bridge a further flow barrier between further planar regions of the device in a further bridging position.

13. The device according to any one of claims 1 to 12, wherein the analytic region comprises a porous layer including at least one of a fibrous material and porous particles.

14. A liquid handling system for an analytical device, wherein the liquid handling system includes an actor structure, a retaining structure, and a biasing structure, wherein the actor structure is configured to act upon a liquid barrier for a liquid when released by the retaining structure, wherein the biasing structure is configured to apply a mechanical force urging the actor structure towards the retaining structure, and wherein the retaining structure is configured to retain the actor structure when in a dry state, and to release the actor structure when in a wet state.

15. A method for performing a chemical analysis, the method comprising: providing a device according to any one of claims 1 to 13; wetting the retaining structure whereby the retaining structure releases the actor structure.

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