The present invention relates to the technical field of distribution valves. More particularly, it relates to a microfluidic distribution valves suitable for laboratory use.
WO2017/037072 describes a rotary microfluidic distribution valve particularly suited for use in an automated flow cytometer. This valve comprises a stator having a plurality of peripheral ports, and a central port connected to a syringe-type pump. A rotor mounted pivotally on the stator comprises at least one conduit which can be used to connect any of the peripheral ports to the central port, depending on the relative angular position between the rotor and the stator. As a result, various fluids can be drawn from the peripheral ports into the syringe-type pump, from where they can subsequently be output to another of the peripheral ports. It is also possible to draw several different fluids into the syringe-type pump, e.g. for carrying out a biological or chemical reaction.
However, when several fluids are drawn into the syringe-type pump simultaneously, it is difficult to ensure that they are well-mixed in order to carry out a biological or chemical reaction under homogeneous conditions. Better mixing would require attaching an external mixing chamber to a fluid port, which is bulky, expensive and will result in long fluid transit distances through the connecting conduits, which is particularly problematic in the case of very small samples. In such a case, long conduits lead to fluid losses and complications with cleaning and/or sterilisation.
An aim of the present invention is hence to at least partially overcome the above-mentioned drawbacks.
More specifically, according to a first aspect, the invention relates to a distribution valve as defined in claim 1. This valve comprises:
According to the invention, the said stationary element comprises a mixing chamber in fluidic communication with one of said first fluid ports. In other words, this chamber is enclosed within the structure of the stationary element.
As a result, mixing can take place within the valve structure itself, rather than in a pump or in an external mixing chamber. The mixing can take place by creating turbulence in the chamber by operating the pump, or by means of at least one mixing element (see below). The system is thus compact, and the conduits leading to the mixing chamber are kept as short as possible. This latter aspect helps with cleaning, minimises wastage of samples, and so on, and reduces (or even eliminates) dead volume.
According to a second aspect, the distribution valve comprises:
According to this aspect of the invention, said movable element comprises a mixing chamber in (permanent or selective) fluidic communication with said at least one second port and arranged to be brought into fluidic communication with at least one of said first ports. In other words, the mixing chamber is formed within the structure of the movable element such that it can be made to connect the second port to at least one of the first ports. The movable element may comprise a further connecting conduit arranged to fluidically connect the second port to one of the first ports, but in its absence, such fluidic communication can simply pass through the mixing chamber.
Again, mixing can take place within the valve structure itself, rather than in a pump or in an external mixing chamber. The mixing can take place by creating turbulence in the chamber by operating the pump, or by means of at least one mixing element (see below). The system is thus compact, and the conduits leading to the mixing chamber are kept as short as possible. This latter aspect helps with cleaning, minimises wastage of samples, reduces or eliminates dead volume, and so on.
Advantageously, said mixing chamber had a cross-sectional area at least five times as large as the cross-sectional area of one of said conduits. This provides enough volume and cross-sectional area to enable sufficient mixing to take place.
Advantageously, at least one mixing element is positioned inside said mixing chamber. This mixing element can e.g. be a mechanical agitator such as a plunger-type stirrer, at least one magnetically-attractable pellet or bead (e.g. made of a ferromagnetic or ferrimagnetic material, and optionally encapsulated e.g. in a polymer such as PTFE). The use of such an active mixing element permits good mixing of even relatively viscous fluids, and/or of mixtures with a very high volume ratio difference (i.e. a large proportion of one component and a small proportion of a second component). It also permits fast mixing, and a reduction of reagent volume.
In the case in which the at least one mixing element is at least one magnetically-attractable pellet or bead, the one of the stationary element and the movable element which does not contain the mixing chamber comprising a magnet or an electromagnet arranged to magnetically couple with said at least one magnetically-attractable pellet or bead. In other words, if the mixing chamber is in the stationary element, the (electro)magnet is in the movable element, and if the mixing chamber is in the movable element, the (electro)magnet is in the stationary element. Hence, by simply moving the movable element with respect to the stationary element while the (electro)magnet is mechanically coupled with the magnetically-attractable pellet or bead, this latter can be moved within the mixing chamber and create turbulence to “stir” the fluid therein. Alternatively, one or more electromagnets may be situated adjacent to the mixing chamber, so as to be able to move the mixing element by magnetic coupling. Typically, the magnet or electromagnet is fixed in relation to the element in which it is incorporated (whether it be the stationary element or the movable element according to the case in question), but it can also be movable with respect thereto.
Advantageously, the movable element may be arranged to rotate with respect to said stationary element, or may be arranged to translate with respect thereto, along one or more translational axes.
Advantageously, a heating element may be arranged adjacent to at least one wall of said mixing chamber, so as to be able to use the mixing chamber for incubating samples while a chemical or biological reaction takes place.
Advantageously, an adaptor for attaching a plurality of hoses may be positioned on said stationary element and is arranged such that at least some of said hoses are in fluidic communication with corresponding first ports.
Advantageously, and notably in the case in which the valve bearing surfaces are planar, at least part of the volume of said mixing chamber, preferably at least 25% of its volume, preferably at least 50% of its volume, preferably at least 75% of its volume, preferably substantially all of its volume is situated within a locus defined by extending the outer peripheral wall of said movable element through the thickness of the stationary element. In the case in which the movable element translates, the minimum percentage can hold in all translational positions, or only in certain positions, whereas in the case in which the movable element rotates about an axis, this will typically hold at all times unless the movable element is non-cylindrical (e.g. cut away on one or more sides), in which case the same considerations as for a translational element may apply. In any case, this allows a particularly compact construction.
Further details of the invention will appear more clearly upon reading the description below, in connection with the following figures which illustrate:
The valve 1 comprises a first, stationary, element 3, intended to be attached to a support by means of bolts or similar. A plurality mounting holes, lugs or similar may be provided to this effect, if required. The stationary element 3 comprises a first valve bearing surface 5 on a first surface thereof, illustrated here as being the upper surface. A second, movable, element 7 is provided, which comprises a second valve bearing surface 9 in contact with this first valve bearing surface 5, the materials used for these surfaces being chosen and finished to such a degree that they are sealed one to the other except where required to enable fluidic communication (see below). For instance, the first valve bearing surface 5 should ideally be polished, and is ideally made from a relatively hard material such as glass, silicon, silica, ceramic, glass-ceramic, stainless steel or similar, or from a softer material with a relatively hard coating like diamond-like carbon, alumina, silica or similar. The second valve bearing surface 9 is ideally made of a softer, relatively low-friction material such as PTFE, PEEK, nylon or similar, or can be a harder material as mentioned above coated with PTFE, PEEK, nylon or similar. Or, these materials can be reversed, the harder materials forming the second valve bearing surface 9 and the softer materials forming the first valve bearing surface 5. In both cases, the first and second valve bearing surfaces 5, 9 will then seal to each other aside from where ports interface with each other, without requiring further sealing means. However, other materials are possible, and conventional seal arrangements can be used.
In the illustrated embodiment of
First valve bearing surface 5 comprises a plurality of fluid ports 11a, 11c which emerge at corresponding openings provided in said surface 5. These ports 11 are of two types: a first type 11a, a number of which lead to conduits 11b which are each in fluid connection with a corresponding channel of an adaptor 13 arranged to permit the attachment of hoses to the first ports 11a (see
The second valve bearing surface 9 of the movable part 7 comprises a connecting conduit 15 arranged to be able to connect any of the first ports 11a to the second port 11c, depending on the position of the movable element 7 with respect to the stationary element 3. Since in the illustrated embodiment the movable element 7 is adapted to rotate about its central axis 7a with respect to the stationary element 3, the connecting conduit 15 is simply a radial groove extending from the centre of rotation with sufficient length so as to be able to interface with any of the first ports 11a (see
In any case, the connecting conduit fluidically connects the first port 11a in question with the second port 11c simultaneously, thereby providing a continuous and contiguous flowpath therebetween. This is clearly distinct from a situation in which a movable conduit is used to “shuttle” aliquots of fluid from one port to the next as is the case in document US2009/129981. In this latter case, there is no continuous flowpath between the two ports at any time.
When the angular position of the movable element 7 with respect to the stationary element 3 causes the connecting conduit 15 to overlap a first port 11a, this latter is then fluidically connected with the second port 11c, and fluid can be drawn from that first port 11a, through the connecting conduit 15, and into the second port 11c, or vice-versa. This second port 11c itself forms a short, axial conduit 11m, which opens into an interface 17 adapted to be connected to a bi-directional pump 31 such as a syringe-type pump or any other convenient type of pump (see
According to this embodiment of the invention, at least one of the first ports 11a is connected to the corresponding channel of the adaptor 13 via a mixing chamber 19, visible in
Mixing chamber 19 is formed as a cavity in the stationary element 3, and is in fluidic communication with one of the first ports 11a via a first conduit 11d, and with the adaptor 13 by means of a further conduit 11f. Each of these conduits 11d, 11f emerges proximate to a respective, opposite, end of the mixing chamber 19 via a corresponding port 11g, which does not emerge at the first valve bearing surface 5 but simply causes the corresponding conduit 11d, 11f to open into the mixing chamber 19. Mixing chamber 19 has a cross-sectional area at least five times, preferably at least 10 times, as great as the conduit 11d leading to it, considered in any of its median planes and compared with the lateral cross-sectional area of the conduit 11d. Mixing chamber 19 typically has a volume of between 0.01 mL and 1 mL, preferably between 0.05 mL and 0.5 mL. Ideally, the mixing chamber 19 is contained entirely within the footprint of the movable element 7, i.e. is entirely overlapped by this latter. In other words, if one were to define a locus extending the outer peripheral wall of the movable element 7 through the thickness of the stationary element 3, the mixing chamber is ideally entirely contained within this cylindrical locus, which is particularly compact. Different shapes of movable element 7 will, of course, result in differently-shaped loci. However, it is also possible that the mixing chamber 19 is only partially within this locus (e.g. at least 25%, preferably at least 50%, further preferably at least 75% of its volume is situated within the locus). This same principle can also apply to a translational movable element 7 (see the description of
It should further be noted that, rather than having a conduit 11d fluidically connecting one of the first ports 11a to the mixing chamber 19, said first port 11a can open directly into the chamber 19, which applies equally to the embodiment of
By pivoting the movable element 7 so as to align its connecting conduit 15 with a particular first port 11a, fluid can be drawn into a pump connected to the interface 17 from an external source fluidically connected to the corresponding channel in the adaptor 13. The movable element 7 can then be rotated so as to align its connecting conduit 15 with the first port 11a leading to the mixing chamber 19, and the fluid can then be injected into the mixing chamber 19. In other words, depending on the relative angular position of the movable element 7 with respect to the stationary element 3, a first port 11a can be selected and brought into fluidic communication with the second port 11b.
By working the pump in both directions, turbulence can be created in the mixing chamber 19, thereby mixing the fluid therein. Several different fluids from different first ports 11a can be injected sequentially into the mixing chamber 9, and then mixed by generating turbulence as described above. Alternatively, several different fluids from different first ports 11a can be aspirated sequentially into the pump 31 and then injected into the mixing chamber 19 in one operation after placing the movable element 7 in the correct orientation with respect to the stationary element 3 so as to cause the second port 11c to communicate fluidically with the mixing chamber 19.
In order to avoid having to operate the pump backwards and forwards to mix the fluid in the chamber 19, one or more mixing elements 21 can be provided therein. As illustrated, this mixing element is a single magnetically-attractable pellet fitted loosely into the chamber 19, but multiple, smaller pellets or beads are also possible. The magnetically-attractable pellet may for instance be steel or another ferromagnetic metal, a ferrimagnetic ceramic, or other magnetically-attractable material. The pellet may be encapsulated in an inert substance such as glass, a ceramic, or a polymer such as PTFE. In the illustrated embodiment, the pellet is cylindrical, with its longitudinal axis parallel to the axis 7a of the movable element 7 (see
A magnet 23 (see
As illustrated, the chamber 19 extends along an arc of a circle centred on the axis 7a, but it can also extend along a straight line, can be cylindrical, have a square or rectangular cross-section in the plane of the stationary element 3, or have any other convenient shape.
Alternatively, the mixing element 21 may be mechanically actuated, e.g. a plunger-type agitator arrangement passing through a sidewall or the underside of the stationary element 3, as illustrated in
In each case, the mixing element 21 has several advantages. It improves the speed of mixing, permits a reduction of reagent volume, permits mixing liquids with several components in which one component is present in a very small proportion with respect to the other (e.g. one component being <10%, <5% or even <1% by volume of the total liquid present), and permits mixing of even relatively viscous liquids.
In all of these variations, the permeable wall 19a serves to improve turbulence in the fluid in the chamber 19, and thereby to improve mixing and the homogeneity of the fluid once mixed.
In this variant, the movable element 7 is arranged to slide, i.e. translate, along a longitudinal axis with respect to the stationary element 3, and to this end the first ports 11a are arranged in a straight line extending parallel to this longitudinal axis. The second port 11b is formed as a slot also extending along a direction parallel to this longitudinal axis of displacement, and the connecting port 15 provided in the movable element 7 is arranged to be able to bring any of the first ports 11a in fluidic connection with the second port 11b. Again, one of the first ports 11a leads to a mixing chamber 19, which may be of any of the forms discussed above. Again, a mixing element 21 may be provided therein (not illustrated in
The other features of the valve 1 are as before, and need not be described further.
As illustrated, the chamber 19 is connected to a central port 11j of the movable element 7, which is in permanent fluidic communication with the second port 11c of the stationary element 3. Towards its side remote from the central port 11j, the chamber is in fluidic communication with a further port 11k positioned so as to be able to be brought into fluidic communication with one of the first ports 11a according to the relative angular position of the movable element 7 with respect to the stationary element 3. Further port 11k may open directly into the mixing chamber 19 (itself hence forming a conduit), or may be fluidically connected thereto by means of a further conduit.
Furthermore, a conventional connecting conduit 15 is provided as in
As before, the chamber 19 may contain a mixing element 21 of any convenient type (not illustrated in
The same principle of locating the mixing chamber 19 in the movable element 7 can also be applied to the embodiment of
In terms of the construction of the stationary element 3, this can be produced as a unitary, monolithic part, e.g. by additive manufacturing (3D printing, stereolithography, or similar), thereby incorporating all cavities, conduits and ports into a single, unitary construction. Suitable materials are polymers such as acrylic (PMMA), nylon, epoxy, PEEK but also ceramics, glasses, glass-ceramics, stainless steel and so on, and surfaces may be post-machined and coated with a layer of another substance such as PTFE, Parylene or DLC (diamond-like carbon).
However, the embodiment as illustrated in
A second plate 35b is provided upon the first plate 35a, this second plate 35b comprising first ports 11a and the corresponding conduits 11b, 11d, 11f, together with a through-hole for second port 11c. Second plate 35b hence comprises the first valve bearing surface 5. Since the conduits 11b, 11d, 11f extend parallel to the surface of the plate, they can be formed e.g. by irradiation of a transparent material such as a suitable glass by the intersection of two or more lasers, followed by chemical etching of the irradiated channel. This technique is known as laser-induced deep etching (LIDE) or laser-assisted etching, and typically uses a femtosecond laser. Alternatively, the conduits 11b, 11d, 11f can be formed in situ in the case in which the plate is formed by additive manufacturing (3D printing, such as SLM, SLS, stereolithography or similar). Or, the second plate 35b can be formed by two sub-plates in which half of each conduit is machined, etched or laser-ablated as a groove, with the conduit being formed once the two sub-plates are unified by friction welding, laser welding, gluing or similar. The same principle can be applied to a single groove in one plate, the other plate having a flat surface facing the groove. This flat plate could alternatively, for instance, be formed as an adhesive tape bonded to the grooved plate. Both of the first and second plates 35a, 35b are fixed together and to the main body of the stationary element 3, e.g. by gluing, laser welding, friction welding, clamping or similar. The two plates 35a, 35b are constructed such that they are sealed one to the other aside from where fluid pathways are intentionally provided.
Although the invention has been described with reference to specific embodiments, variations thereto are foreseeable without departing from the scope of the invention as defined in the appended claims.
For instance, the valve bearing surfaces 5, 9 do not have to be planar, and can be cylindrical or shaped as a partial cylinder. In such a case, the first ports 11a are distributed circumferentially, and the second port 11b can be arranged as required, e.g. extending parallel to, or even along, the axis of said cylinder. Furthermore, it is also possible to provide multiple mixing chambers 19 in any given distribution valve 1, for instance for dilution purposes or for carrying out multiple different reactions in different chambers simultaneously.
Number | Date | Country | Kind |
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18188767.0 | Aug 2018 | EP | regional |
Filing Document | Filing Date | Country | Kind |
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PCT/EP2019/071210 | 8/7/2019 | WO | 00 |