Patent Description:
Document <CIT> discloses a system for optimising the production performance of a milk producing animal herd, in which chemical analysis means are used which comprise a carrier tape onto which a series of separate and consecutive test strips or dry sticks are arranged, with flush holes inbetween. However, no details of a way to produce same are disclosed.

Document <CIT> discloses a method of producing a test tape for liquid samples, that comprises a transport tape and a plurality of test fields, which can be cut to length by a laser.

It is an object of the present invention to provide a method of producing such a reagent tape in a simple, fast and economical way.

The present invention achieves the above object at least partly by means of a method according to claim <NUM>.

According to the present invention, there is no need to prepare separate test strips or dry sticks, and apply these to a carrier tape. Rather, the reagent pads are applied in one single step, which is very simple and quick to achieve, while the separating step is performed by means of providing a hydrophobic barrier line between the pads. This line prevents that liquid jumps over between neighbouring pads. Thereto, a number of options are available, as will be shown below. Herein, it is advantageous that the reagent is applied as a continuous layer, so that its properties, and in particular its thickness, is controllable within tight margins.

In addition, the hydrophobic barrier line can be made extremely narrow, and thus provide the possibility to obtain reagent pads at a very small mutual distance, that still act as separate pads. This contrasts with a much larger distance that would be required when arranging test strips or dry sticks onto a carrier tape, due to movement and mechanical tolerances. An advantage of this possible very close distance is that the same carrier tape can now carry more pads, such that it will be less often necessary to replace a carrier tape. This is advantageous in automated sampling systems, that do not need human supervision. By having more reagent pads per tape, such a system may work for a longer time without human intervention. Moreover, because of the easy control of a line supply device or a laser ablation beam, it would also be more easily possible to change the settings on the fly even during production of the tape, or to apply different settings on purpose, such as for alternating tests on the tape that require a different reagent area or the like. This increased variability is also an advantage of the present invention.

The production of the tape in all is thus flexible, easy and economical and very fast.

Here it is noted that it is not an obvious step to produce a tape with reagent pads that are so close to each other, at least in desired cases. After all, to ensure that a sample drop can react with the reagent in the pad, the pad should absorb the liquid rather quickly, and the pad will then quickly spread the liquid to the very borders of the pad. When the next pad is very close, chances are that the liquid will spread to the next, neighbouring pad. However, the inventors have found that even at very close range, liquid will not cross the hydrophobic barrier line to the neighbouring pad.

Particular embodiments and advantages are described in the dependent claims, as well in the now following part of the description.

The step of providing a hydrophobic barrier line comprises removing at least a, preferably throughgoing, strip of reagent in a direction transverse to a longitudinal direction of the tape by means of laser ablating. The latter is a very simple and fast step, since a laser beam is easily controlled, such as to the depth of removing material. It is easily possible to set the laser beam such that it removes just all the reagent material in the strip, that is, right down to the base tape layer. Note that it is not always necessary to remove a throughgoing strip of material, if the remaining (reagent) material no longer allows liquid to pass from pad to pad, for example because the remaining material was also altered by the laser beam, such as being burnt or molten liquid-impervious by the laser beam. The mechanism is not yet understood. It could for example be caused by the strip of removed material being, though very narrow, still wider than the required width for capillary action. Alternatively, it could be that the laser beam changes the properties of the material, such that it now repels liquid, or that it even melts close the capillaries near the ablation line. In any case, it was found that even at a small width of, say, a tenth of a millimeter, liquid would not pass from pad to pad. Based on the eventual understanding of the mechanism, it may prove possible to find alternative methods for producing a tape with such reagent pads at close mutual distances. For example, if the key in these embodiments is simply to remove a strip of reagent material, it might suffice to mechanically remove the strip of material, such as by grinding, or by etching, although these methods would probably prove more cumbersome. If the key would be to alter the properties of the material, the use of chemicals, or spot-welding or the like, might also work, although these methods would, again, probably be much more cumbersome than using a laser beam for ablating the material.

Said laser ablating comprises removing between two neighbouring reagent pads two mutually parallel, and preferably throughgoing, strips of the reagent. With this measure, there is now a double barrier between the pads, which even further improves their mutual independence, be it at the cost of the distance between two pads. Still, the production speed and flexibility are improved with respect to known tape production methods. An additional advantage of having a wider distance between two pads is that, when a tape is stored in a cassette that protects unused reagent pads against the environment, such as humidity, dust and light, it is then easier to seal of the unused parts of the tape by means of e.g. a duckbill valve or other means on the cassette. If the pads would be separated by just the strip with a width of the very narrow laser ablation beam, it could be possible for liquid to travel between pads via the sealing surface of the duckbill valve or the like. Alternatively, the duckbill valve or the like would have to have a sealing surface that is at most as wide as the removed strip, which is not only not very realistic, but also prone to wear and tear. Note also that it is alternatively possible, but not according to the present invention, to laser ablate just one, but a wider strip of material, such as with a width of not a tenth of a millimeter but, say, one millimeter. Although this will take longer in most case, it may provide better sealing capabilities due to the absence of reagent material between the reagent pads, and thus a lower local thickness.

In embodiments, the step of providing a hydrophobic barrier line comprises applying a line of hydrophobic material onto and into the reagent layer. Such a line also creates separate pads out of the single continuous layer of reagent material. The hydrophobic nature of the material used for the line ensures that liquid will not pass from one reagent pad to the next. Note that in all of the present invention it is understood that the liquid is a watery liquid, such as in particular milk or blood. Liquids that would not be repelled by the hydrophobic material of the lines, such as possibly molten fats or the like, are expressly excluded.

The hydrophobic material may be a (liquid or liquified) polymer with hydrophobic properties, such as a teflon or teflon-based polymer. Since the hydrophobic material should also prevent the liquid from flowing to a neighbouring pad underneath the line, the material should penetrate into the reagent material to block liquid- flow there as well. The selection of a suitable hydrophobic material thus also depends on the properties of the reagent material, but is readily made in practice. The material may be provided by means of a printer-like device, or simply a nozzle, either line-shaped, movable across the tape or a series of nozzles. The linewidth may be as narrow as one or a few tenths of a millimeter, but may alternatively be made sufficiently wide for sealing by means of a sealing element, cfr. the double laser ablation line described above.

In embodiments, the step of applying reagent comprises applying a plurality of mutually parallel continuous track-like layers of a respective reagent onto the base tape layer. The advantages for a single track of reagent material that is formed into separate pads applies equally well to two or more of such tracks of, preferably, different reagent materials. This allows to produce a tape with a variety of reagent materials easily, quickly and economically. Note that it is not necessary that the pads are all of the same size. For example, it is possible to provide reagent pads for a first reagent material with a first length (i.e. distance between the two limiting strips), while pads of a second reagent material may be given a different second length. This, too, is due to the fact that a laser beam is very easily controlled, and may even be controlled between different tracks of reagent material, of course, in case all pads are given the same length, it is easy to guide the laser ablation beam across all of the tape in one go, possibly switching off the beam when it is above the part of the tape between the different tracks of reagent materials. In all of this, it is possible to apply the various reagent material consecutively or, preferably, simultaneously.

In embodiments, the reagent material and the base tape layer are each provided wound onto a bobbin or the like, wherein the method comprises uniting the reagent material and the base tape layer by simultaneously unwinding the respective bobbins and bringing the reagent material onto the base tape layer. Depending on the properties of the reagent material and/or the base tape layer, it may be advantageous to supply an additional layer for uniting the reagent material and the base tape layer. For example, there may be provided an adhesive layer onto the base tape layer, onto the reagent material or even as a separate material also wound on a bobbin or the like and, in any case, provided between the reagent material and the base tape layer.

In attractive embodiments, the step of applying reagent material comprises providing an application nozzle for supplying the, or each respective, reagent material, and moving the base tape layer passed the, or each, nozzle, to thereby apply the, or each, reagent material as a continuous layer onto the tape. Herein, the, or each, reagent material is supplied from a supply container, through a nozzle, onto the base tape. The reagent material will then be either a fluid itself, or combined with one or more other materials such that the result is an applicable fluid. In all cases, a subsequent step, such as a curing step by means of UV light or the like, to stabilise the reagent material may be applied when needed. Note that it is also possible to supply one or more reagent materials as or in a fluid, and to supply one or more reagent materials from a respective bobbin or the like, i.e. as a solid, tape-like material.

There is also provided, but not according to the invention a reagent tape, that comprises a base tape layer and a series of consecutive and separate reagent pads of a reagent, the tape being produced with a method according to the present invention. Such a tape will have at least some of the advantages described above for the method. In addition, it is to be remarked that in use of the tape, the average centre-to-centre distance of the pads can be made smaller than in existing reagent tapes. This makes it possible to move the tape quicker. In particular shifting the reagent tape according to the invention over one reagent pad length takes less time than similarly moving a known tape, in each case with the same speed. Thus, either a higher throughput or a similar throughput with lower speed and thus lower forces is achievable according to the invention.

There is also provided, but not according to the invention a milking device with a milk sampling device, the milking device arranged to draw milk from a dairy animal, wherein the milk sampling device comprises an analyser with a reagent tape as disclosed herein, and a sampler supply a milk sample from the milk drawn from the dairy animal to a reagent pad of the reagent tape, the analyser being arranged to analyse said at least part of the milk sample for the presence of at least one substance by observing a change in said reagent pad. As indicated above, the present invention offers the advantage that more reagent pads may be provided on a tape, and thus the milk sampling device may work for a longer period without human intervention, in particular for chaning the tape. This advantage is particularly useful for milking stalls in which the dairy animals walk about freely and in which the milking device is a robotic milking device with one or more milking robots. In such milking stalls, it cannot be predicted when the next animal will be milked, and thus neither when the next sampling is needed. Therefore, human operators or human intervention is minimal in such milking stalls, and thus the advantage of the milk sampling device being able to work for a prolonged period is important here.

The invention will now be elucidated by way of a number of exemplary embodiments and the drawings, in which.

<FIG> shows a diagrammatic representation of a milking system <NUM> for milking teats <NUM> of an udder <NUM> of a dairy animal. The milking system <NUM> comprises teat cups <NUM>, connected to short milk lines <NUM>, debouching in a milk jar4, that in turn is connected to a main milk line <NUM>. A milk pump is denoted <NUM>, and a three-way valve with <NUM> connects to a bulk tank line <NUM> connected to a bulk milk tank <NUM>, and to a sewer line <NUM>.

A milking robot <NUM> has a robot arm <NUM> and a robot control unit <NUM>. A sampling unit is generally denoted <NUM>, and a sampling line <NUM> with an optional sample valve <NUM>. The sampling unit <NUM> comprises a supply reel <NUM>-<NUM> and a collecting reel <NUM>-<NUM> for a tape <NUM> with reagent pads <NUM>. A nozzle device for sample droplets is denoted by <NUM>, a light source <NUM> emits light <NUM>, and a camera is denoted by <NUM>.

In use of the milking system <NUM>, the robot control unit <NUM> controls the milking robot <NUM> with the robot arm <NUM> to attach the teat cups <NUM> to the teats <NUM> of the udder <NUM> of a dairy animal such as a cow. The milk that is subsequently milked leaves the teat cups <NUM> under the influence of a vacuum, that is applied by a pump not depicted here, via the short milk lines <NUM>, and is collected in a milk jar <NUM>.

In order to comply with legal requirements, the first milk from each teat must be tested for physical changes, and if desired for other deviant properties. This can be done by means of a separate foremilk test device, or it can be done with the help of the sampling unit <NUM> as supplied according to the invention. Then use will be made of the alternative sample lines <NUM>'. In case of a negative assessment, the milked milk collected in the milk jar <NUM> will then be pumped to the sewer line <NUM> by means of the milk pump <NUM>, via the main milk line <NUM> and the three way valve <NUM>. All these devices are under the control of the robot control unit <NUM>. Contrarily, if the milk is assessed to be OK, it will be pumped to the bulk milk tank <NUM> via the bulk line <NUM>.

It is also possible that the sampling unit <NUM> takes a sample from the milk jar <NUM>, in particular a mixed sample from milk that was milked from all teats and during all of the milking. This helps to get a good assessment of the milk that (if not rejected based on the foremilk assessment or otherwise, such as being antibiotics milk) will be sent to the bulk tank <NUM>, or possible to one of several bulk milk tanks. For example, the milk from different cows could be sent to different bulk tanks, based on their fat content, their protein content or otherwise, as determined by the sampling unit <NUM>. In such embodiments, as the one shown in <FIG>, the sample line <NUM> runs from the milk jar <NUM> to the sampling unit <NUM>, and optionally has a sample valve <NUM>. Note that the latter could also be a part internal to the sampling unit <NUM>.

Most often, however, the sampling unit <NUM> is used to determine a property of the milk from a cow, either per teat quarter <NUM> or for the whole udder <NUM>/animal, which property is subsequently used in animal management but not for immediate control of the milk destiny. Examples are the measurement of hormones such as progesterone, that play a role in the reproductive cycle of the animal, or of substances that relate to feeding or metabolic health of the animal. Based on the assessment by the sampling unit <NUM>, the farmer or the control unit <NUM> may then adapt feeding, call a veterinary for a health check or for insemination, and so on.

A sampling unit <NUM> is very generally shown further, in that it here contains a supply reel <NUM>-<NUM> and a collecting reel <NUM>-<NUM>, between which a tape <NUM> is wound down by means of non-shown tape mover means, such as a cassette deck motor or stepper motor. The tape <NUM> carries reagent pads <NUM> that contain reagent that gives a detectable response in the presence of a defined substance, often the intensity of the response depending on the concentration of the substance brought into the reagent via the sample droplet. Such a sample droplet is delivered via the nozzle <NUM>. A light source <NUM> then shines light <NUM> onto the reagent pad <NUM>, and a camera <NUM> observes the response, if any, in the reagent pad. The light source <NUM> may be any suitable light source, such as one or more LEDs, and the emitted light <NUM> may be visible light, UV(A) radiation, (near) infrared, and so on, depending on the used reagent. Of course, the camera <NUM> should be adapted to detect radiation coming from the reagent pad <NUM>. Often, this is reflected or scattered light, but it could be different radiation, such as fluorescence radiation. In any case, details of such radiation and detection may easily be implemented by the skilled person and do not form the present invention as such.

It is remarked here that the camera <NUM> and the light source <NUM> are shown below the tape <NUM> with the reagent pads <NUM>. In practice, it may also occur, and in fact often be advantageous, if the camera <NUM> and the light source <NUM> are positioned above the tape <NUM>. This allows the camera to image the reagent pad to which the sample droplet is supplied without advancing the tape, i.e. immediately. In addition, there is no risk of any liquid, or dirt, falling from the reagent pad to the camera and/or light source. Moreover, in general, it is advantageous if the camera <NUM> and/or the light source <NUM> are positioned outside the sampling unit <NUM>, or rather outside a housing of the sampling unit. The camera and the light source are still functional parts of the sampling unit as a whole, but the former two parts are positioned outside a housing with the tape (reels) and the supply nozzle <NUM>.

<FIG> diagrammatically show two embodiments of the method according to the present invention in a side view.

To begin with <FIG>, it shows a first reel <NUM> with blank tape material <NUM>, a second reel with adhesive material <NUM>, and a third reel <NUM> with reagent material <NUM>. Also shown are pressing rollers <NUM>.

A reservoir <NUM> with a nozzle device <NUM> sprays hydrophobic barrier material <NUM>. The final result is wound onto the supply reel <NUM>-<NUM>, cfr. the supply reel in <FIG>. With brackets A, and B, the part of the tape with a continuous layer of reagent, and the part with separate reagent pads, respectively, have been indicated.

The method shown here provides for making a tape with separate reagent pads in a simple, fast and reliable way. It starts with blank tape reel <NUM>, from which blank tape material <NUM> is unrolled in a direction of the arrow shown. Then, in an optional step, adhesive material <NUM> is unrolled from a second reel <NUM>, and guided to the blank tape material <NUM>, after which they are pressed together with the help of, optionally heated, rollers <NUM>-<NUM>. In a next step, reagent material <NUM> is unrolled from a third reel <NUM>, and guided to the blank tape - adhesive combination, and these are pressed together by the, optionally heated, rollers <NUM>-<NUM>. What is now obtained is a tape material <NUM> with a continuous layer of reagent <NUM> thereon, if desired with an adhesive layer <NUM> inbetween.

In a next step, a nozzle device <NUM> sprays hydrophobic barrier material <NUM>, from a reservoir <NUM>, onto the reagent layer <NUM>, in the form of barrier lines. These barrier lines separate reagent pads from each other, because the (watery) sample liquids will not cross the hydrophobic barrier lines. Thus, in part B of the drawing, there are separate reagent pads, while in part A there is still a continuous layer of reagent <NUM>. For the nozzle device <NUM>, it may be advantageous to use a position controlled nozzle, a set of parallel nozzles or the like, such as those that are used in (inkjet) printers. However, any type suffices, as long as the nozzle device <NUM> is able to apply the material <NUM> in the form of a line or the like. The hydrophobic material <NUM> may also be selected from several known materials, such as paraffine or TFE polymers. The choice may depend on whether the reagent material <NUM> allows the hydrophobic material to penetrate downto the layer therebeneath (adhesive <NUM>, if any, the blank tape material <NUM>, or any other layer provided beneath the reagent layer <NUM>).

<FIG> shows an advantageous alternative embodiment of the method, in which similar parts are denoted with hyphened reference numerals. Thus, a blank tape <NUM>' is unrolled from a supply reel <NUM>', in the direction of the arrow. A reservoir <NUM> holds reagent material <NUM> that is sprayed by nozzle <NUM>. A laser device <NUM> emits a laser beam <NUM>. the finished tape is rolled onto the reel <NUM>'-<NUM>.

In this embodiment, the blank tape <NUM>' is coated with a layer of reagent material <NUM> by spraying it onto the tape with a nozzle <NUM>. Herein, the reagent material <NUM> is often a combination of a pure reagent, such as an enzyme, with some additive to make it sprayable, such as a solvent. Other methods of applying the reagent material <NUM> are also possible, such as a contact roller or the like, as long as a continuous layer is obtained.

Subsequently, the continuous layer of reagent material is divided into separate reagent pads by means of a controllable laser beam <NUM> from a laser device <NUM>. The laser beam <NUM> removes a thin strip of reagent material from the tape <NUM>', and thereby creates a laser ablation line, or alters the properties of at least a border region of the pads, all this such that a drop of sample liquid will not go from one reagent pad to a neighbouring pad. The finished tape is then rolled up onto the reel <NUM>'-<NUM>. Again, the part of the tape with the continuous layer of reagent material is indicated with "A", and the part with the separate reagentpads is indicated with "B".

<FIG> diagrammatically show in a top view two embodiments of the method according to the present invention. In particular, <FIG> shows a top view of the embodiment of <FIG>. From the right, a blank tape <NUM>' is unrolled from the reel <NUM>', and is then provided with a continuous layer <NUM> of reagent material. Then the controllable laser beam provides lasewr ablation lines <NUM> to make separate reagent pads <NUM>. These lines <NUM> can be made very narrow, down to about <NUM> if desired. this allows the reagent pads <NUM> to be very closely spaced, so that each tape <NUM>' can have many, many pads. This in turn allows a prolonged use of one and the same tape <NUM>'; without human intervention, such as for exchanging the tape.

<FIG> shows a top view of an alternative embodiment. Here, the <NUM>" is wider, and has room for two parallel tracks of reagent materials <NUM>-<NUM> and <NUM>-<NUM>, that are supplied to the tape consecutively, although it could be possible to provide them at the same time, i.e. in parallel. Note that the embodiment of <FIG> might serve to provide this method, when the material <NUM> would not be an adhesive below the reagent material, but would be another reagent material next to reagent material <NUM>.

However provided, the reagent materials <NUM>-<NUM> and <NUM>-<NUM> are present as parallel, continuous tracks or layers. Again, these tracks are divided into separate pads <NUM>-<NUM> and <NUM>-<NUM>, respectively, by means of a laser beam. Here, however, the beam does not provide single laser ablation lines between the pads, but pairs <NUM> of laser ablation lines. This not only further improves the liquid barrier properties between the consecutive pads, but also allows sealing with a sealing means onto the pads without forming a bridge for liquid between two pads. It is noted that this also means that the consecutive pads <NUM> are spaced less closely as a consequence of allowing sealing. Yet, the spacing may still be narrow, while the invention as a whole still allows extremely narrow spacing.

<FIG> diagrammatically show a detailed close-up view of a embodiments of a tape as disclosed herein, but not according to the present invention. <FIG> diagrammatically shows a finished tape with the base tape layer <NUM>', with reagent pads <NUM> on top, separated by laser ablation lines <NUM> and <NUM>'. Also indicated are material layers <NUM> and <NUM>.

The material layers <NUM> are believed to be present in some cases, although applicant does not wish to be tied to this or any other application. The laser beam, that is used to remove the reagent material in order to provide a laser ablation line <NUM> and form pads <NUM>, heats up the reagent material and evaporates it. However, it could be that reagent material in the layer <NUM> next to the removed material is heated up only so far as to melt and seal itself. This then changes the properties of the reagent layer, since that should allow liquid to penetrate through the material, in order for a sample droplet to reach the true reagent (enzyme or the like) in the reagent material. It could be that the layer <NUM> actually becomes impervious to the liquid, to support the liquid barrier properties of the laser ablation line. The same (as yet untested) hypothesis holds for the layer <NUM> at the bottom of the laser ablation line <NUM>. If indeed the properties are changed such that that layer <NUM> does not allow liquid to go through, it suffices for it to remain present at the bottom of the laser ablation line. In other words, it is then not necessary for the laser beam to remove any and all material down to the blank base tape material <NUM>'. However, it is stressed here that this is just a theory to explain the observed phenomenon of liquid barrier properties of a laser ablation line between reagent pads <NUM>.

To the right in the <FIG>, there is shown another laser ablation line <NUM>', in which all reagent material actually has been removed downto the blank base tape material layer <NUM>'. It is clear that no liquid will go from one reagent pad <NUM> t oa neighbouring pad.

<FIG> diagrammatically shows a detailed close-up view of a another embodiment of a tape as disclosed herein, but not according to the present invention. Here, there is no laser ablation line, but the liquid barrier line between neighbouring reagent pads <NUM> is now formed by means of applying a hydrophobic barrier material in a narrow zone <NUM>, such as with the method described for <FIG>. It can be seen that in principle there still a continuous layer <NUM>' of reagent material. However, because a hydrophobic barrier material such as a teflon-like polymer has been applied onto and into that layer <NUM>', in the form of a barrier line <NUM>, still separate reagent pads <NUM>' have been formed. It is possible that the zone or line <NUM> protrudes somewhat above the layer <NUM>', which in fact might even help as an additional liquid barrier between the pads <NUM>'.

Claim 1:
Method of producing a reagent tape, that comprises a base tape layer (<NUM>; <NUM>'; <NUM>") and a series of consecutive and separate reagent pads (<NUM>) of a reagent, for use in a milk sampling device (<NUM>),
the milk sampling device being arranged to supply a droplet of a milk sample onto one of the reagent pads on the tape in order to produce a response in the reagent to detect a presence or concentration of a substance in the milk sample,
the method comprising
- providing the base tape layer (<NUM>; <NUM>'; <NUM>") of the reagent tape,
- applying onto the base tape layer a continuous layer (<NUM>; <NUM>; <NUM>-<NUM>, <NUM>-<NUM>) of the reagent,
- dividing the supplied continuous reagent layer into separate reagent pads (<NUM>) by providing a hydrophobic barrier line (<NUM>, <NUM>; <NUM>) between said pads,
wherein said step of providing a hydrophobic barrier line comprises removing between two neighbouring reagent pads two mutually parallel, and preferably throughgoing, strips of the reagent in a direction transverse to a longitudinal direction of the tape by means of laser ablating.