WO2020070493A1 - Fluid analyser and sensor cassette - Google Patents

Fluid analyser and sensor cassette

Info

Publication number
WO2020070493A1
WO2020070493A1 PCT/GB2019/052778 GB2019052778W WO2020070493A1 WO 2020070493 A1 WO2020070493 A1 WO 2020070493A1 GB 2019052778 W GB2019052778 W GB 2019052778W WO 2020070493 A1 WO2020070493 A1 WO 2020070493A1
Authority
WO
WIPO (PCT)
Prior art keywords
cassette
fluid
analyser
sensor
sensors
Prior art date
Application number
PCT/GB2019/052778
Other languages
French (fr)
Inventor
Toby Mottram
Original Assignee
Milkalyser Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GBGB1904836.2A external-priority patent/GB201904836D0/en
Application filed by Milkalyser Limited filed Critical Milkalyser Limited
Publication of WO2020070493A1 publication Critical patent/WO2020070493A1/en

Links

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366Apparatus specially adapted for solid-phase testing
    • G01N33/54386Analytical elements
    • G01N33/54387Immunochromatographic test strips
    • G01N33/54388Immunochromatographic test strips based on lateral flow
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5023Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures with a sample being transported to, and subsequently stored in an absorbent for analysis
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01JMANUFACTURE OF DAIRY PRODUCTS
    • A01J5/00Milking machines or devices
    • A01J5/013On-site detection of mastitis in milk
    • A01J5/0131On-site detection of mastitis in milk by analysing the milk composition, e.g. concentration or detection of specific substances
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01JMANUFACTURE OF DAIRY PRODUCTS
    • A01J5/00Milking machines or devices
    • A01J5/013On-site detection of mastitis in milk
    • A01J5/0135On-site detection of mastitis in milk by using light, e.g. light absorption or light transmission
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N21/78Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a change of colour
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/02Food
    • G01N33/04Dairy products
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483Physical analysis of biological material
    • G01N33/487Physical analysis of biological material of liquid biological material
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366Apparatus specially adapted for solid-phase testing
    • G01N33/54386Analytical elements
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00009Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with a sample supporting tape, e.g. with absorbent zones
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00009Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with a sample supporting tape, e.g. with absorbent zones
    • G01N2035/00019Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with a sample supporting tape, e.g. with absorbent zones cassette structures
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1079Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices with means for piercing stoppers or septums

Definitions

  • This invention relates to a fluid analyser for biological fluids such as water, blood, milk or urine as well as a sensor cassette for the same.
  • biological fluids such as water, blood, milk or urine
  • biomarkers that can be indicators of biological activity, and animal health or fertility. Measuring the concentration of these biomarkers and relaying the information for example via wireless data communications and the internet is an increasing requirement for modern precision management and warning systems, particularly in animal healthcare and process control.
  • a specific example of the need for improvement is in the measurement of progesterone in milk.
  • alternative applications and embodiments of the invention could be used where a fluid stream was to be analysed for example, river water for disease biomarkers, wash water in poultry processing for signs of Campylobacter or salmonella, or toilet water being examined for signs of a disease.
  • a suitable lateral flow immunosensor with colorimetric change for that application exists.
  • An example of a fluid analyser according to the invention measures progesterone from milk in a milking parlour.
  • the concentration of progesterone in milk can be used as a means of detecting the onset of oestrus, infertility and pregnancy in the cow from whom the milk is extracted.
  • This invention makes the automated measurement of progesterone in milk a low cost and routine process.
  • Progesterone is one such hormone and changes in its concentration are associated with several key stages in the ovulation cycle.
  • One particularly important change is the drop in progesterone concentration which normally precedes oestrous and occurs prior to ovulation. Measuring the drop in progesterone can help to understand when ovulation will occur and when the most appropriate insemination time is, as well as detecting pregnancy and non-pregnancy.
  • progesterone is found in relatively high concentrations which can make detection and accurate measurement easier.
  • One known system combines automated sampling and five sensing systems including one for progesterone in milk.
  • the system automatically measures the level of progesterone in milk, software indicates insemination time, lists animals for final pregnancy confirmation, indicates early abortion, and lists the cows with risk of cysts and prolonged anoestrus. Studies claim that a number of farms using the system have stopped performing manual pregnancy tests and saved between €250 and €350 per cow per year.
  • This prior art system consists of a large analyser, boxed with a controlled environment and complex plumbing system to bring the milk samples from the short milk tubes to the analyser. It is designed to fit into parlours with a small number of milking points when newly installed and is difficult to retrofit into existing parlours, particularly in large systems that are working continuously. This is a key limitation of the prior art system.
  • Another limitation of the above system is that it requires extensive plumbing to bring milk to a central temperature controlled analyser.
  • the system uses a plurality of analytes but most of the valuable information to predict ovulation is contained in the measurement of progesterone.
  • progesterone In itself it uses analogue progesterone measurements, but this is unnecessary since the concentration of progesterone above or below a set threshold, is the key measurement.
  • a further need is for equipment that can supply data into a variety of analytical systems with models adapting to changing circumstances and desired management requirements.
  • the present invention provides a fluid analyser comprising: means for receiving a fluid to be analysed; a cassette driving mechanism for receiving, in use, a cassette comprising an array of sensors; an optical detecting system comprising a camera and a light source; a cassette driving mechanism for selectively driving, in use, sensors on the cassette through the optical detecting system such that it passes between the camera and the light source; and a fluid delivery mechanism for delivering, in use, fluid to be analysed to the sensor prior to the sensor passing through the detecting system such that, when the sensor passes through the optical detecting system, the output of the optical can provide an output indicative of the biological composition of the fluid.
  • the present invention also provides a cassette comprising an array of sensors, each sensor comprising a sealed liquid receiving compartment having a lateral flow immunosensor.
  • the cassette may further have a chemical modifier such as a desiccant tablet contained therein.
  • the immunosensor is a biosensor which detects the formation of an antigen-antibody complex, and converts this into a detectable format.
  • the immunosensor may be of the type which produces a colour change which can then be read by an optical analyser that may include image processing.
  • the present invention provides a method of operating the above system and a method of analysing fluid using the above cassette and/or system.
  • the requirements for a biological monitoring system are that it can easily fitted to a variety of existing installations, that it measures the target analyte above or below a given threshold and provides data through an open interface.
  • This invention meets those requirements.
  • milking systems are highly automated to ensure a high number of cows can be milked one or more times per day. Any new system of automatically measuring biomarkers in milk must link to the existing parlour automation to know which cow is to be analysed and in which milking position.
  • Most milking parlours operate near continuously and so time to install analysers, plumbing, vacuums, as well as other services pipes, lines, wires, and connections must be minimised or removed.
  • the requirement is for a system that can be installed in minutes and use as few connections as possible for fluids, power, and data.
  • the invention provides an automated ovulation, infertility, and pregnancy detection system for dairy animals, that requires no external wiring or plumbing. It can be fitted in minutes by attaching the box in a level position to a rigid surface adjacent to the cow, cutting the long milk tube and connecting the cut ends to the entry and exit pipes.
  • Any progesterone system must be capable of being fitted to any milking system with a minimum service requirement. If it uses a lateral flow immunosensor it can only be used once as the biochemical reactions cannot be reversed.
  • a number of sensors are needed to map the fertility status. The number of sensors required per cow, per year can vary from about 12 to 50 according to the prior art. Due to variability in calving pattern and the quasi random distribution of cows at each milking point during milking it is difficult to predict the rate of use of sensors in any given milking stall. Thus, a system which replenishes sensors is important.
  • a cassette of sensors should only need to be changed between milkings, meaning that the number of sensors in a cassette should be as many as the maximum number of cows that can be milked at any milking stall during a milking period.
  • the size of a cassette of sensors can be set as a minimum of 25 sensor strips but the cassette is designed such that it can be daisy chained together into modules of 50, 75 or any size determined by the space available.
  • Alternative examples can use smaller sizes of cassettes and greater multiples of them joined together depending on the service interval for the system.
  • cassettes moisture may enter the package and degrade the performance of the lateral flow immunosensor.
  • the cassette is formed of polyethylene terephthalate (PET), or other formable material, with a low permeability and at a thickness that permits it to be formed into a flexible strip. This allows it to be capable of being pushed into a radius to minimise the space required for storage before and after use in the system.
  • PET polyethylene terephthalate
  • the cassette can define plural individual pockets with a sensor in each.
  • a desiccant feature to extend the storage life.
  • the sensor is sealed into each depression, which is created by a shaping method, for example thermoforming, the PET or other formable material and is bonded under tension to an impermeable laminated membrane.
  • the membrane can be punctured by a hollow needle assembly which creates a small well as the base of the sensor.
  • the shape of the cassette sensor pockets can permit a rack and pinion assembly, or the edges of the bended pack can be used, for a pinch roller or punctured sprocket assembly.
  • This invention is a refinement of the system disclosed in WO 2017/144913 which provides a cassette of sensors packaged to hold milk on a sensor and a camera to capture an image of the colour change of a lateral flow immunosensor.
  • a sample of milk was to be analysed the package containing the individual sensor was ruptured and the sample injected onto the sensor tip.
  • the invention can illuminate the sensor from one side and capture the image from the other.
  • the sensor image is captured with transmission of light, which reduces reflection from the cassette and other internal surfaces as in the prior art system.
  • This embodiment is further improved by alteration of the lighting arrangement to illuminate the whole sensor allowing the colour change to be more accurately captured.
  • the image capture mechanism can be refined further using apertures when necessary between the camera and sensor in order to capture a high-quality image of the active region of the sensor.
  • This embodiment has two benefits, the full depth of colour change through the sensor matrix is captured and the reflections from the surface of the packaging are removed.
  • the quantity of fluid discharged into the sensor package and onto the sensor is controlled to reduce residue.
  • the volume discharged is around 100 microlitres and may be in the range of 100 to 200 microlitres appropriate to the size and density of the lateral flow chemistry, this is sufficient to activate the sensor without excess and can be completely absorbed by the sensor strip.
  • the fluid is discharged slowly, a couple of millimetres above the sensor surface so that the meniscus bridge, or other method of connecting the fluid and surface, draws the fluid into the sensor by capillary action.
  • Desiccant capsules within the sensor cassette removes any surplus moisture depriving microbes of the opportunity to grow.
  • the dessicant is also essential in preventing microbial degradation of sensors in the cassette particularly if they are to be used or stored over a prolonged period. A preservative may be added also.
  • the system disclosed in this application can feature a double moisture barrier with desiccants included within each barrier and features of the analyser design to ensure dry operation.
  • the external barrier of the cassette is a package, preferably of foil or other suitable material, containing the cassette with a desiccant.
  • a notch holds a desiccant tablet in place and close to the sensor. The sensors are loaded into the package in clean, dry conditions by hand or robot and sealed until use.
  • Figure 1 is a view of the analyser in a system according to the invention
  • Figure 2 is a view of the internal components of the analyser of figure 1 ;
  • Figure 3 is a schematic diagram showing the milk line connections and double peristaltic pump mechanism of the system of the invention.
  • Figure 4 is a plan cross sectional view of the analyser of figure 1 ;
  • FIG. 5 shows detail of the lighting and image capture system employed in an example of the invention
  • Figures 6A and B show the carriage mechanism in both the active and waiting positions;
  • Figure 7 shows a sensor cassette module in accordance with the invention.
  • Figure 8 shows a sprocket drive mechanism which may be used in the system of the invention
  • Figure 9 shows an alternative example of the invention which allows to change in the form factor of the analyser
  • Figures 10 to 12 show a more detailed example of the analyser of figure 9 , with minor variations thereto in terms of its internal working and drive structure;
  • Figures 13 to 19 show yet a further example analyser in key stages in its operation during insertion and removal of a cassette.
  • FIG 1 there is shown a fluid analyser 1 and system suitable for installation in any milking system conforming to ISO 5707.
  • Preferred examples of the invention combine a number of features that provide an automated sampler/analyser for direct retrofitting to existing milking parlours. The principal features are shown in the figures.
  • the analyser 1 of the invention is arranged to receive a cassette 2 which contains one or more individually packaged sensors 5 with blisters 4.
  • the cassette 2 is shown in detail in figure 7 and comprises one or more discrete compartments 3 within a single thermo vacuum formed blister 4, each compartment 3 has a sensor strip 5 and a desiccant tablet 6 and is then sealed by a closure film.
  • the cassette 2 may be constructed such that the region around each sensor strip 5 is optically transparent to improve optical reading and analysis of the sensor strip after the analyte (in this case milk) has been applied to it.
  • the sensor material itself may also be supported by a transparent substrate to further improve optical characteristics, Mylar is an example material that can be provided to achieve this substrate.
  • Each cassette may be housed in a secondary package (not shown) for longer term storage.
  • the cassette 2 is shown as a flat package, but may be rolled as shown in figures 10 and 11 to provide a more compact device.
  • the cassette 2 may have other additional features, such as a leading edge which is the first point to be inserted into the analyser 1 and which contains an indicator for position referencing or sensor alignment, with that indicator being, for example, an opaque leading edge which can be detected by the sensor, and which may include an optical read hole for reference alignment.
  • Other features can be provided to ensure engagement with any rack and pinion configuration or to provide referencing of position as required.
  • the cassette 2 is inserted into the main analyser 1 through a slot 7 which resides beneath a closure lid 8.
  • Other approaches to insertion are possible and are emitted in the later examples.
  • the cassette 2 interfaces with a drive mechanism 9 which is indexed forward by means of a motor driven lead screw arrangement 10 to a piercing/dispensing location 11.
  • a ratchet mechanism (not shown) may replace the lead screw to reduce space required.
  • the drive mechanism 9 is a motor driven sprocket which engages directly with the cassette 2.
  • the analyser 1 is attached to a milk line by a rotatable take-off point pipe connection 12 through which protrudes a dip tube 13 connected to a non return valve 14 between pump P1 15 and pump P2 16. This is positioned to minimize the residual milk in the dip tube 13.
  • the output from pump P1 15 is mechanically and fluidly connected to a main carriage 17 which is raised and lowered by means of further leadscrew/motor arrangement 18.
  • the main carriage 17 has a low position in which pumps P1 15 and P2 16 draw fluid from an on-board flush tank 19 to purge the internal feed lines and a needle 20.
  • milk line flush solution from the milk line can be drawn up through the dip tube 13 and fed around the system, again, cleaning the entire feed line.
  • This mechanism can also be used to top up the tank 19 with fluid from the milk line when it is being flushed, though, as shown, the tank 19 can also be topped up manually.
  • the needle 20 in an upper carriage position the needle 20 is deployed to a pierce and dispense position. Milk is then drawn up through the dip tube 13 and fed through needle 20 to the compartment 3. After a predetermined time, the carriage 17 returns to its low (start) position where an internal flush with fluid from tank 19 can take place and the sensing cycle can then be repeated when required.
  • the system is arranged such that a digital camera 21 with a suitable focal length points to the area of the sensor 5 where the biochemical reactions create a colour change.
  • the scene is illuminated from the depressed side of the cassette 2 by a light emitting diode 22 or equivalent so that the full optical density of the biochemical reactions can be captured by the camera 21.
  • An aperture 23 the same shape and width as the sensor 5 prevents excess light from the LED 22 from entering the camera 21.
  • the components of system which provide the optical sensing system are shown in figure 5.
  • a sensor mount 30 is shown in combination with a camera mount 31 and light guide 32. This structure provides the aperture 23. In use the camera 21 is attached and this structure is placed in the system such that sensors 5 in the cassette 2 are driven therethrough when required.
  • a controlled volume, in the range of 50 to 250 microlitres, of the liquid to test is injected onto the sensor 5 using meniscus dosing or other method to avoid any surplus liquid being left to decompose. All the liquid is absorbed by the sensor 5 and rendered inert by this process. This prevents contamination of the system by unused sample fluid.
  • the needle 20 Whilst the sensor 5 is absorbing the liquid and registering the colour change the needle 20 is retracted and a wash pump 24 used to rinse away residues to a drain (not shown).
  • the cassette 2 is then indexed to the next position to provide a fresh sensor 5 ready for the next test.
  • the system 1 may have an on board processor which receives the output of the camera 21 and analyses it to provide an indication of the result of the sensor 5 and test fluid interaction.
  • the system 1 can have means for transmitting the output to an external and remote processing component that can perform the necessary analysis.
  • the system 1 may have an onboard control system which can communicate the need to maintain the system, replace the cassette or the existence of any error state to a user.
  • FIG. 9 an alternative example of the invention is shown, with components which correspond to those of the earlier examples being numbered identically.
  • the cover 8 retains the cassette 2 in position and is structured to have a twist lock mechanism when it is placed over the main body of the analyser 1.
  • This example can be adapted with the capability to provide a larger number of sensors per cassette or multiple connected cassettes.
  • the cassette is flexible, with used sensors being rolled up after use.
  • the cassette 2 is loaded from the top and a cassette loading piece 35 provided to retain the shape of the cassette 2 during loading.
  • FIG 10 shows the example analyser with the cassette 2 exposed by removal of a closure lid 8 which is shown in Figures 11 and 12.
  • the structure allows a large number of sensor components to be provided on the cassette 2 yet provides a simple robust insertion mechanism of low footprint.
  • Milk is drawn into the analyser 1 through milk line connection 12 as in the other examples, and an optical sensor component 5 is also provided.
  • the closure 8 and cassette 2 is driven by a central rotating drive mechanism which engages with the enclosure 8 when it is in position and rotates the cassette 2 around the analyser rim.
  • FIG. 12 shows the analyser components exposed and in an inverted position, a pump module 24 is again provided to draw in liquid and provide washing, together with provision of a drain 29 which allows washed and spilt fluids to be drained out from the analyser 1 to reduce contamination and the build-up of sour milk which can cause unpleasant odours and clogging of the system.
  • a processor 28 can be provided to provide a control module for operation of the system and to process and/or forward data for analysis.
  • the drive mechanism in this case may allow the enclosure 8 to be driven by a central drive 27 which engages with the enclosure 8 and a drive motor via an internal enclosure component 26.
  • the drive motor rotates both the internal enclosure component 26 and the enclosure 8 to move a sensor cassette 2 through the sensor component 5 as desired. Provision of the additional internal enclosure 26 reduces the possibility of contamination of the analyser 1 during changing of cassettes, as this is often done in harsh environments such as a milking parlour.
  • the analyser 1 has a receiving slot 4 a cassette housing 41 comprising a cassette 2 in accordance with the examples described previously.
  • On end of the cassette housing 41 is surrounded by a seal to prevent internal contamination, but this has been shown removed from these figures for ease of understanding.
  • a user removes a seal on the external cassette 41 exposing one end of the internal cassette 2, which is then inserted into the slot 40 in the analyser 1.
  • the exposed end of the cassette 2 engages with rollers 42 and is drawn into the interior of the analyser 1.
  • Using a roller mechanism 42 has some advantages over the pin and ratchet mechanism shown in the other examples, in that it can retain the cassette firmly and accurately, particularly if it is used in conjunction with indexing which it is possible to provide on the cassette 2.
  • a support spool 46 which can assist in alignment of an individual sensor blister 4 for piercing by the needle 20 but also can be structured to support the sensor blister 4 during the piercing to improve accuracy of that piercing.
  • Figure 16 shows a spool container 42 which is placed over the opening 40 in the analyser 1. It is constructed, in this example, with ribs so that it cannot rotate out of alignment, and is then retained in position by a bezel 43 as shown in Figure 17. Tests can then be performed in a manner similar to that of previous examples on individual sensors in the cassette 2, with the sensor closest to the aperture 41 being used first. The testing process, including piercing, application of milk, and optical analysis etc. is the same as in the previous examples. When a sensor has been used the cassette 2 can be advanced into the spool container 42 as shown in Figures 18A and 18B.
  • each of the example analysers may have a cassette detection switch to ensure that operation does not occur unless a valid cassette has been inserted correctly, and all may provide, as outlined above, a flushing system to clean the system between operations and/or between replacement of cassettes, or at regular time intervals.
  • All of the examples may also provide additional features such as a heater to optimise the heat of individual samples during measurement to provide for consistent data output.
  • a heater to optimise the heat of individual samples during measurement to provide for consistent data output.
  • Such a configuration may also comprise temperature and/or humidity measurement to provide feedback control to the heater to optimise measurement temperature.
  • the heater can be provided in a predetermined area to heat sensors immediately prior to or after insertion of milk to optimise temperature, preferably controlling the temperature during sensing to around 38°C.
  • the analyser 1 may be arranged to move sensors following insertion of milk to a region where they sit, optionally to be heated, for a predetermined time to ensure adequate reaction with the sensor analyte before being moved to be read. This can optimise measurements by ensuring adequate reaction times, but also enables the capture of additional milk samples in additional sensors whilst waiting for the optimum reaction time to have passed, ensuring continued operation of the analyser 1 even in circumstances where reaction times for individual sensors are longer than the times between individual cows being milked at an associated analyser position.

Abstract

A fluid analyser comprises means for receiving a fluid to be analysed. There is a cassette driving mechanism for receiving, in use, a cassette comprising an array of sensors. An optical detecting system comprises a camera and a light source and a cassette driving mechanism selectively drives in use, sensors on the cassette through the optical detecting system such that it passes between the camera and the light source. A fluid delivery mechanism delivers, in use, fluid to be analysed such that, when the sensor passes through the optical detecting system, the output of the optical detecting system can provide an output indicative of the biological composition of the fluid.

Description

FLUID ANALYSER AND SENSOR CASSETTE
This invention relates to a fluid analyser for biological fluids such as water, blood, milk or urine as well as a sensor cassette for the same. Such fluids carry biomarkers that can be indicators of biological activity, and animal health or fertility. Measuring the concentration of these biomarkers and relaying the information for example via wireless data communications and the internet is an increasing requirement for modern precision management and warning systems, particularly in animal healthcare and process control.
A specific example of the need for improvement is in the measurement of progesterone in milk. However, alternative applications and embodiments of the invention could be used where a fluid stream was to be analysed for example, river water for disease biomarkers, wash water in poultry processing for signs of Campylobacter or salmonella, or toilet water being examined for signs of a disease. The only requirement being that a suitable lateral flow immunosensor with colorimetric change for that application exists.
An example of a fluid analyser according to the invention measures progesterone from milk in a milking parlour. The concentration of progesterone in milk can be used as a means of detecting the onset of oestrus, infertility and pregnancy in the cow from whom the milk is extracted. This invention makes the automated measurement of progesterone in milk a low cost and routine process.
Extensive research into reproduction and fertility in cows throughout the latter half of the 20th century defined the role of a variety of hormones in the ovulation cycle in cattle. Progesterone is one such hormone and changes in its concentration are associated with several key stages in the ovulation cycle. One particularly important change is the drop in progesterone concentration which normally precedes oestrous and occurs prior to ovulation. Measuring the drop in progesterone can help to understand when ovulation will occur and when the most appropriate insemination time is, as well as detecting pregnancy and non-pregnancy. When compared to other hormones in milk, progesterone is found in relatively high concentrations which can make detection and accurate measurement easier.
The measurement of progesterone concentration in bodily fluids, including milk, has been possible since the late 1960’s. Development of improved assays through the 1990’s took the process out of the laboratory and allowed farmers to perform progesterone analysis cow-side. Progesterone analysis is not common on modern farms due to time-consuming nature of sampling and testing milk regularly by hand. However, production of an immunosensor in the form of a lateral flow assay (LFA), now provides a quick and accurate way to measure progesterone concentration in milk on-site. An evaluation of this assay found a sensitivity for detecting corpus luteum of 90.1% and a specificity of 98.7%. They concluded that the use of cow-side progesterone assays can improve the reproductive performance of a herd when used appropriately.
Recently new sensors and technologies have been developed to further aid the measurement of progesterone from milk. These include improved immunoassays and competitive inhibition assays, experimentation with near-infrared reflectance spectroscopy and aquagrams, as well as technologies which improve the performance of existing progesterone assays. However, despite some promising results, these developments fail to address the need to automate the process of progesterone analysis.
One known system combines automated sampling and five sensing systems including one for progesterone in milk. The system automatically measures the level of progesterone in milk, software indicates insemination time, lists animals for final pregnancy confirmation, indicates early abortion, and lists the cows with risk of cysts and prolonged anoestrus. Studies claim that a number of farms using the system have stopped performing manual pregnancy tests and saved between€250 and €350 per cow per year.
One study used the system on a herd of 60 cows for a year, concluding that the system was a useful tool for reproductive management in this herd (S. Leonardi et al. 2013, Use of a proactive herd management system in a dairy farm of northern Italy: technical and economic results. Journal of Agricultural Engineering, 44 (s2): e41). Several reproductive indices were improved including: a reduction in days open from 166 to 103 days, improvements in both conception and pregnancy rates (from 40% to 64% and 18% to 61 % respectively), and a reduction in the days from 1st and 2nd insemination from 45 to 28 days. In addition, by using a basic economic model a five-year return on investment was determined following installation in this case study. This prior art system consists of a large analyser, boxed with a controlled environment and complex plumbing system to bring the milk samples from the short milk tubes to the analyser. It is designed to fit into parlours with a small number of milking points when newly installed and is difficult to retrofit into existing parlours, particularly in large systems that are working continuously. This is a key limitation of the prior art system.
Another limitation of the above system is that it requires extensive plumbing to bring milk to a central temperature controlled analyser. The system uses a plurality of analytes but most of the valuable information to predict ovulation is contained in the measurement of progesterone. In itself it uses analogue progesterone measurements, but this is unnecessary since the concentration of progesterone above or below a set threshold, is the key measurement. A further need is for equipment that can supply data into a variety of analytical systems with models adapting to changing circumstances and desired management requirements.
The present invention provides a fluid analyser comprising: means for receiving a fluid to be analysed; a cassette driving mechanism for receiving, in use, a cassette comprising an array of sensors; an optical detecting system comprising a camera and a light source; a cassette driving mechanism for selectively driving, in use, sensors on the cassette through the optical detecting system such that it passes between the camera and the light source; and a fluid delivery mechanism for delivering, in use, fluid to be analysed to the sensor prior to the sensor passing through the detecting system such that, when the sensor passes through the optical detecting system, the output of the optical can provide an output indicative of the biological composition of the fluid.
The present invention also provides a cassette comprising an array of sensors, each sensor comprising a sealed liquid receiving compartment having a lateral flow immunosensor. The cassette may further have a chemical modifier such as a desiccant tablet contained therein. The immunosensor is a biosensor which detects the formation of an antigen-antibody complex, and converts this into a detectable format. In the invention the immunosensor may be of the type which produces a colour change which can then be read by an optical analyser that may include image processing. The present invention provides a method of operating the above system and a method of analysing fluid using the above cassette and/or system. The requirements for a biological monitoring system are that it can easily fitted to a variety of existing installations, that it measures the target analyte above or below a given threshold and provides data through an open interface. This invention meets those requirements. In the modern dairy, milking systems are highly automated to ensure a high number of cows can be milked one or more times per day. Any new system of automatically measuring biomarkers in milk must link to the existing parlour automation to know which cow is to be analysed and in which milking position. Most milking parlours operate near continuously and so time to install analysers, plumbing, vacuums, as well as other services pipes, lines, wires, and connections must be minimised or removed. The requirement is for a system that can be installed in minutes and use as few connections as possible for fluids, power, and data. The invention provides an automated ovulation, infertility, and pregnancy detection system for dairy animals, that requires no external wiring or plumbing. It can be fitted in minutes by attaching the box in a level position to a rigid surface adjacent to the cow, cutting the long milk tube and connecting the cut ends to the entry and exit pipes.
Any progesterone system must be capable of being fitted to any milking system with a minimum service requirement. If it uses a lateral flow immunosensor it can only be used once as the biochemical reactions cannot be reversed. During a cow’s lactation cycle a number of sensors are needed to map the fertility status. The number of sensors required per cow, per year can vary from about 12 to 50 according to the prior art. Due to variability in calving pattern and the quasi random distribution of cows at each milking point during milking it is difficult to predict the rate of use of sensors in any given milking stall. Thus, a system which replenishes sensors is important. Given that disruption to milking is best avoided, a cassette of sensors should only need to be changed between milkings, meaning that the number of sensors in a cassette should be as many as the maximum number of cows that can be milked at any milking stall during a milking period. In the invention the size of a cassette of sensors can be set as a minimum of 25 sensor strips but the cassette is designed such that it can be daisy chained together into modules of 50, 75 or any size determined by the space available. Alternative examples can use smaller sizes of cassettes and greater multiples of them joined together depending on the service interval for the system.
One issue with cassettes is that moisture may enter the package and degrade the performance of the lateral flow immunosensor. In a preferred embodiment the cassette is formed of polyethylene terephthalate (PET), or other formable material, with a low permeability and at a thickness that permits it to be formed into a flexible strip. This allows it to be capable of being pushed into a radius to minimise the space required for storage before and after use in the system.
The cassette can define plural individual pockets with a sensor in each. Within each sensor pocket, preferably at the top of the sensor, is a desiccant feature to extend the storage life. The sensor is sealed into each depression, which is created by a shaping method, for example thermoforming, the PET or other formable material and is bonded under tension to an impermeable laminated membrane. The membrane can be punctured by a hollow needle assembly which creates a small well as the base of the sensor. The shape of the cassette sensor pockets can permit a rack and pinion assembly, or the edges of the bended pack can be used, for a pinch roller or punctured sprocket assembly.
This invention is a refinement of the system disclosed in WO 2017/144913 which provides a cassette of sensors packaged to hold milk on a sensor and a camera to capture an image of the colour change of a lateral flow immunosensor. When a sample of milk was to be analysed the package containing the individual sensor was ruptured and the sample injected onto the sensor tip.
This prior art system only captures the colour change in the top layers of the sensor and can in some circumstances give an underestimate of the amount of colour change. Secondly the package reflects the illuminating light which causes the image processing software embedded in the microprocessor unnecessary processing, as unwanted image artefacts must be removed.
To improve the image capture mechanism, the invention can illuminate the sensor from one side and capture the image from the other. The sensor image is captured with transmission of light, which reduces reflection from the cassette and other internal surfaces as in the prior art system. This embodiment is further improved by alteration of the lighting arrangement to illuminate the whole sensor allowing the colour change to be more accurately captured. The image capture mechanism can be refined further using apertures when necessary between the camera and sensor in order to capture a high-quality image of the active region of the sensor. This embodiment has two benefits, the full depth of colour change through the sensor matrix is captured and the reflections from the surface of the packaging are removed.
In the system of WO 2017/144913 the amount of milk used for analysis is not controlled and can fill the reservoir at the bottom of each cassette pocket. As the cassette may not be changed for an extended period, the residual milk which is not absorbed by the sensor is likely to be degraded by microbial action causing issues of smell and contamination.
In this invention the quantity of fluid discharged into the sensor package and onto the sensor is controlled to reduce residue. The volume discharged is around 100 microlitres and may be in the range of 100 to 200 microlitres appropriate to the size and density of the lateral flow chemistry, this is sufficient to activate the sensor without excess and can be completely absorbed by the sensor strip. The fluid is discharged slowly, a couple of millimetres above the sensor surface so that the meniscus bridge, or other method of connecting the fluid and surface, draws the fluid into the sensor by capillary action. Desiccant capsules within the sensor cassette removes any surplus moisture depriving microbes of the opportunity to grow. The dessicant is also essential in preventing microbial degradation of sensors in the cassette particularly if they are to be used or stored over a prolonged period. A preservative may be added also.
The system disclosed in this application can feature a double moisture barrier with desiccants included within each barrier and features of the analyser design to ensure dry operation. The external barrier of the cassette is a package, preferably of foil or other suitable material, containing the cassette with a desiccant. In addition, within each sensor pocket a notch holds a desiccant tablet in place and close to the sensor. The sensors are loaded into the package in clean, dry conditions by hand or robot and sealed until use.
The box containing the system is waterproofed with the slot for inserting and removing a sensor cassette covered by a waterproof lid, assembly is interlocked to prevent the system operating with the lid open. Examples of the present invention will now be described with reference to the accompanying drawings, in which: Figure 1 is a view of the analyser in a system according to the invention;
Figure 2 is a view of the internal components of the analyser of figure 1 ;
Figure 3 is a schematic diagram showing the milk line connections and double peristaltic pump mechanism of the system of the invention;
Figure 4 is a plan cross sectional view of the analyser of figure 1 ;
Figure 5 shows detail of the lighting and image capture system employed in an example of the invention;
Figures 6A and B show the carriage mechanism in both the active and waiting positions; Figure 7 shows a sensor cassette module in accordance with the invention;
Figure 8 shows a sprocket drive mechanism which may be used in the system of the invention; Figure 9 shows an alternative example of the invention which allows to change in the form factor of the analyser;
Figures 10 to 12 show a more detailed example of the analyser of figure 9 , with minor variations thereto in terms of its internal working and drive structure; and
Figures 13 to 19 show yet a further example analyser in key stages in its operation during insertion and removal of a cassette.
Referring to figure 1 , there is shown a fluid analyser 1 and system suitable for installation in any milking system conforming to ISO 5707. Preferred examples of the invention combine a number of features that provide an automated sampler/analyser for direct retrofitting to existing milking parlours. The principal features are shown in the figures. The analyser 1 of the invention is arranged to receive a cassette 2 which contains one or more individually packaged sensors 5 with blisters 4.
The cassette 2 is shown in detail in figure 7 and comprises one or more discrete compartments 3 within a single thermo vacuum formed blister 4, each compartment 3 has a sensor strip 5 and a desiccant tablet 6 and is then sealed by a closure film. The cassette 2 may be constructed such that the region around each sensor strip 5 is optically transparent to improve optical reading and analysis of the sensor strip after the analyte (in this case milk) has been applied to it. The sensor material itself may also be supported by a transparent substrate to further improve optical characteristics, Mylar is an example material that can be provided to achieve this substrate. Each cassette may be housed in a secondary package (not shown) for longer term storage. In figure 7 the cassette 2 is shown as a flat package, but may be rolled as shown in figures 10 and 11 to provide a more compact device. The cassette 2 may have other additional features, such as a leading edge which is the first point to be inserted into the analyser 1 and which contains an indicator for position referencing or sensor alignment, with that indicator being, for example, an opaque leading edge which can be detected by the sensor, and which may include an optical read hole for reference alignment. Other features can be provided to ensure engagement with any rack and pinion configuration or to provide referencing of position as required.
In this example the cassette 2 is inserted into the main analyser 1 through a slot 7 which resides beneath a closure lid 8. Other approaches to insertion are possible and are emitted in the later examples.
The cassette 2 interfaces with a drive mechanism 9 which is indexed forward by means of a motor driven lead screw arrangement 10 to a piercing/dispensing location 11. A ratchet mechanism (not shown) may replace the lead screw to reduce space required. In an alternative arrangement, which is also space-saving shown in figure 8, the drive mechanism 9 is a motor driven sprocket which engages directly with the cassette 2. One of the benefits of these structures is that they hold the cassette and sensors therein firmly such that, when the sensor is punctured by the needle 20, as described below, there is no distortion of the sensor, improving the accuracy of the measurement. As shown in figure 3, the analyser 1 is attached to a milk line by a rotatable take-off point pipe connection 12 through which protrudes a dip tube 13 connected to a non return valve 14 between pump P1 15 and pump P2 16. This is positioned to minimize the residual milk in the dip tube 13.
The output from pump P1 15 is mechanically and fluidly connected to a main carriage 17 which is raised and lowered by means of further leadscrew/motor arrangement 18.
The main carriage 17 has a low position in which pumps P1 15 and P2 16 draw fluid from an on-board flush tank 19 to purge the internal feed lines and a needle 20.
In addition, with the main carriage 17 in its low position, as shown in figure 6B (at this point the needle 20 is still in its retracted position) and with pump P1 15 running, milk line flush solution from the milk line can be drawn up through the dip tube 13 and fed around the system, again, cleaning the entire feed line. This mechanism can also be used to top up the tank 19 with fluid from the milk line when it is being flushed, though, as shown, the tank 19 can also be topped up manually.
As shown in figure 6A, in an upper carriage position the needle 20 is deployed to a pierce and dispense position. Milk is then drawn up through the dip tube 13 and fed through needle 20 to the compartment 3. After a predetermined time, the carriage 17 returns to its low (start) position where an internal flush with fluid from tank 19 can take place and the sensing cycle can then be repeated when required.
The system is arranged such that a digital camera 21 with a suitable focal length points to the area of the sensor 5 where the biochemical reactions create a colour change. The scene is illuminated from the depressed side of the cassette 2 by a light emitting diode 22 or equivalent so that the full optical density of the biochemical reactions can be captured by the camera 21. An aperture 23 the same shape and width as the sensor 5 prevents excess light from the LED 22 from entering the camera 21. The components of system which provide the optical sensing system are shown in figure 5. Here a sensor mount 30 is shown in combination with a camera mount 31 and light guide 32. This structure provides the aperture 23. In use the camera 21 is attached and this structure is placed in the system such that sensors 5 in the cassette 2 are driven therethrough when required. In operation a controlled volume, in the range of 50 to 250 microlitres, of the liquid to test is injected onto the sensor 5 using meniscus dosing or other method to avoid any surplus liquid being left to decompose. All the liquid is absorbed by the sensor 5 and rendered inert by this process. This prevents contamination of the system by unused sample fluid.
Whilst the sensor 5 is absorbing the liquid and registering the colour change the needle 20 is retracted and a wash pump 24 used to rinse away residues to a drain (not shown).
No liquid is returned to the milk line to avoid contamination of the milking system.
After the image is captured the cassette 2 is then indexed to the next position to provide a fresh sensor 5 ready for the next test.
The system 1 may have an on board processor which receives the output of the camera 21 and analyses it to provide an indication of the result of the sensor 5 and test fluid interaction. Alternatively or in addition, the system 1 can have means for transmitting the output to an external and remote processing component that can perform the necessary analysis. In either case, the system 1 may have an onboard control system which can communicate the need to maintain the system, replace the cassette or the existence of any error state to a user.
Referring to figures 9 , an alternative example of the invention is shown, with components which correspond to those of the earlier examples being numbered identically. In figure 9 there is shown an example with the same functionality but of reduced size through the use of a flexible cassette 2 and ratchet drive mechanism for the cassette 2. In this example the cover 8 retains the cassette 2 in position and is structured to have a twist lock mechanism when it is placed over the main body of the analyser 1. This example can be adapted with the capability to provide a larger number of sensors per cassette or multiple connected cassettes. Here, again, the cassette is flexible, with used sensors being rolled up after use. The cassette 2 is loaded from the top and a cassette loading piece 35 provided to retain the shape of the cassette 2 during loading.
. Figure 10 shows the example analyser with the cassette 2 exposed by removal of a closure lid 8 which is shown in Figures 11 and 12. As with the example of Figure 9, the structure allows a large number of sensor components to be provided on the cassette 2 yet provides a simple robust insertion mechanism of low footprint. Milk is drawn into the analyser 1 through milk line connection 12 as in the other examples, and an optical sensor component 5 is also provided. In this example however the closure 8 and cassette 2 is driven by a central rotating drive mechanism which engages with the enclosure 8 when it is in position and rotates the cassette 2 around the analyser rim. As can be seen from Figure 12, this shows the analyser components exposed and in an inverted position, a pump module 24 is again provided to draw in liquid and provide washing, together with provision of a drain 29 which allows washed and spilt fluids to be drained out from the analyser 1 to reduce contamination and the build-up of sour milk which can cause unpleasant odours and clogging of the system. As with the other examples a processor 28 can be provided to provide a control module for operation of the system and to process and/or forward data for analysis.
The drive mechanism in this case may allow the enclosure 8 to be driven by a central drive 27 which engages with the enclosure 8 and a drive motor via an internal enclosure component 26. The drive motor rotates both the internal enclosure component 26 and the enclosure 8 to move a sensor cassette 2 through the sensor component 5 as desired. Provision of the additional internal enclosure 26 reduces the possibility of contamination of the analyser 1 during changing of cassettes, as this is often done in harsh environments such as a milking parlour.
Referring to Figure 13, in this example the analyser 1 has a receiving slot 4 a cassette housing 41 comprising a cassette 2 in accordance with the examples described previously. On end of the cassette housing 41 is surrounded by a seal to prevent internal contamination, but this has been shown removed from these figures for ease of understanding. In use, a user removes a seal on the external cassette 41 exposing one end of the internal cassette 2, which is then inserted into the slot 40 in the analyser 1. The exposed end of the cassette 2 engages with rollers 42 and is drawn into the interior of the analyser 1. Using a roller mechanism 42 has some advantages over the pin and ratchet mechanism shown in the other examples, in that it can retain the cassette firmly and accurately, particularly if it is used in conjunction with indexing which it is possible to provide on the cassette 2. However, as with the alternative examples it is possible to use a ratchet mechanism or pinch rollers in this example also. It should be noted that the other examples can, of course, use the pinching roller mechanism 42 described herein. Through rotation of the roller mechanism 42 the cassette is drawn into the main body of the analyser 1 as shown in Figures 14A and 14B and figure 15. The cassette 2 is drawn into a second container 45 in this example as shown in figure 14A for storage before use. After use the cassette 2 is expelled for disposal as shown in figure 14B. This example also shows a bezel 43 for retention of spool container 47. Also shown is a feature which may be present in any of the examples, that of a support spool 46 which can assist in alignment of an individual sensor blister 4 for piercing by the needle 20 but also can be structured to support the sensor blister 4 during the piercing to improve accuracy of that piercing.
Figure 16 shows a spool container 42 which is placed over the opening 40 in the analyser 1. It is constructed, in this example, with ribs so that it cannot rotate out of alignment, and is then retained in position by a bezel 43 as shown in Figure 17. Tests can then be performed in a manner similar to that of previous examples on individual sensors in the cassette 2, with the sensor closest to the aperture 41 being used first. The testing process, including piercing, application of milk, and optical analysis etc. is the same as in the previous examples. When a sensor has been used the cassette 2 can be advanced into the spool container 42 as shown in Figures 18A and 18B. When a cassette has been used completely it has been rolled in its entirety back into the spool container 42, at which point a user can remove the retaining bezel 43, withdraw the spool container 42 with the used cassette 2 contained therein and the process of insertion of a new, unused, cassette 2 then being repeated.
With all the above examples there are additional features that may be employed to improve yet further the operation of the analyser 1 and the accuracy of the measurements made by the analyser 1 in use. For example, all may use an injection mechanism to inject milk into individual sensors following piercing of those sensors. The injection mechanism can be controlled to dispense small, regulated amounts of milk, for example in the range of 100 to 150 pl_. Each of the example analysers may have a cassette detection switch to ensure that operation does not occur unless a valid cassette has been inserted correctly, and all may provide, as outlined above, a flushing system to clean the system between operations and/or between replacement of cassettes, or at regular time intervals.
All of the examples may also provide additional features such as a heater to optimise the heat of individual samples during measurement to provide for consistent data output. Such a configuration may also comprise temperature and/or humidity measurement to provide feedback control to the heater to optimise measurement temperature. The heater can be provided in a predetermined area to heat sensors immediately prior to or after insertion of milk to optimise temperature, preferably controlling the temperature during sensing to around 38°C.
In all the examples the analyser 1 may be arranged to move sensors following insertion of milk to a region where they sit, optionally to be heated, for a predetermined time to ensure adequate reaction with the sensor analyte before being moved to be read. This can optimise measurements by ensuring adequate reaction times, but also enables the capture of additional milk samples in additional sensors whilst waiting for the optimum reaction time to have passed, ensuring continued operation of the analyser 1 even in circumstances where reaction times for individual sensors are longer than the times between individual cows being milked at an associated analyser position.
In all the examples of the present invention it is also possible to provide different analytes in different sensors within a single cassette 2. By appropriate control sensors within the analyser 1 , through movement of the cassette 2 under control to processing components, different analysis can be performed to detect different analytes through use of a single sensor cassette 2 and analyser 1 combination, which can ensure flexibility of operation for the end user, as well as enabling the detection of more than one analyte in a simple and effective way using the same device.
As will be appreciated, all the above examples provide a system which is easy to maintain, which reduces contamination, and which also provides more accurate analysis results through improved optical measurement.

Claims

1. A cassette comprising an array of sensors, each sensor comprising a sealed liquid receiving compartment having a lateral flow immunosensor contained therein.
2. A cassette according to claim 1 , wherein the immunosensor is a colormetric immunosensor.
3. A cassette according to claim 1 or 2, wherein each compartment further comprises a desiccant.
4. A cassette according to any preceding claim, wherein the desiccant is positioned in a region of the compartment separate from the immunosensor.
5. A cassette according to any preceding claim, the cassette being constructed such that, in use, it can be inserted into an analyser and engage with a drive mechanism in the analyser to drive the sensors through the analyser.
6. A cassette according to any preceding claim wherein some of the sensors contain immunosensors which are sensitive to analytes which differ to the analytes to which the immunosensors in other sensors are sensitive.
7. A fluid analyser comprising: means for receiving a fluid to be analysed; a cassette driving mechanism for receiving, in use, a cassette comprising an array of sensors; an optical detecting system comprising a camera and a light source; a cassette driving mechanism for selectively driving, in use, sensors on the cassette through the optical detecting system such that it passes between the camera and the light source; and a fluid delivery mechanism for delivering, in use, fluid to be analysed such that, when the sensor passes through the optical detecting system, the output of the optical detecting system can provide an output indicative of the biological composition of the fluid.
8. A fluid analyser according to claim 7, wherein the fluid delivery system comprises a needle which pierces the sensor in use to deliver fluid to be analysed to the sensor through the needle.
9. A fluid analyser according to claim 8, arranged such that, during fluid delivery, a meniscus advanced from the needle extends to touch the sensor surface, allowing capillary action to draw the liquid into the sensor matrix without leaving a residue of sample in the analyser.
10. A fluid analyser according to any of claims 7 to 9, further comprising means for providing cleaning fluid to clean the analyser between measurements.
11. A fluid analyser according to any of claims 7 to 10, wherein the cassette driving mechanism comprises rollers which engage with the cassette.
12. A fluid analyser according to any of claims 7 to 11 , wherein the optical detecting system comprises an aperture having a shape corresponding to that of a sensor and positioned between the camera and a sensor placed in the analyser in use, such that only light that has passed through the sensor is received by the camera.
13. A fluid analyser according to any of claims 7 to 13, further comprising a heater arranged to heat at least a portion of the cassette to a predetermined temperature.
14. A fluid analyser according to any of claims 7 to 13 arranged such that, in use, it can selectively move the cassette such that individual sensors which have received a fluid can be positioned in a resting location for a predetermined time period prior to being driven to the optical detecting system.
15. A fluid analyser according to any of claims 7 to 14 arranged to receive and drive a cassette according to any of claims 1 to 6.
16. A fluid analysing system comprising an analyser according to any of claims 7 to 15 and a cassette according to any of claims 1 to 6.
17. A fluid analysing method comprising the steps of: delivering a fluid to be analysed to a fluid analysing system according to claim 16, receiving an output from the optical detecting system and determining the amount of an analyte in the fluid from the received optical detecting system output.
PCT/GB2019/052778 2018-10-02 2019-10-02 Fluid analyser and sensor cassette WO2020070493A1 (en)

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US20030211619A1 (en) * 2002-05-09 2003-11-13 Lorin Olson Continuous strip of fluid sampling and testing devices and methods of making, packaging and using the same
WO2015073878A1 (en) * 2013-11-15 2015-05-21 Ur Diet, Llc Real-time satiety biofeedback
WO2017144913A1 (en) 2016-02-26 2017-08-31 Milkalyser Limited Milk analyser system and method

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Publication number Priority date Publication date Assignee Title
US5965458A (en) * 1992-12-29 1999-10-12 Oy Medix Biochemica A.B. Test strip, its production and use
US20030211619A1 (en) * 2002-05-09 2003-11-13 Lorin Olson Continuous strip of fluid sampling and testing devices and methods of making, packaging and using the same
WO2015073878A1 (en) * 2013-11-15 2015-05-21 Ur Diet, Llc Real-time satiety biofeedback
WO2017144913A1 (en) 2016-02-26 2017-08-31 Milkalyser Limited Milk analyser system and method

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Title
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