System for determining the validity of lateral flow test results

Abstract

A system (10) for determining the validity of the results of a lateral flow test, the system comprising a lateral flow stick (180a, 180b, 180c). The lateral flow stick (180a, 180b, 180c) comprises: a sample pad (310); a conjugate pad (315) comprising antibody-treated gold particles; and a porous membrane (320) for receiving a capillary flow of a milk sample. The porous membrane (320) comprises: a test line (360) treated with a progesterone reference, the progesterone reference binding to the antibody-treated gold particles of the milk sample and thereby causing the test line (360) to change color when exposed to milk having a progesterone level below a threshold limit; and a control line (370) treated with an antibody reference binding to an antibody and thereby causing the control line (370) to change color when exposed to milk comprising antibody-treated gold particles. The system also includes a sensor (210) and a control unit (150), the control unit being configured to: obtain a reference hue (380) of the control line (370); determine a current hue of the control line (370) based on an image captured by the sensor (210) during the ongoing lateral flow test; compare the reference hue (380) of the control line (370) with the current hue of the control line (370); and indicate the validity of the lateral flow test performed on the lateral flow stick (180a, 180b, 180c) based on the comparison performed.

Description

Technical Field

[0001] This document discloses a system. More specifically, a system for determining the validity of a lateral flow test result performed on a lateral flow stick arranged to indicate progesterone in a milk sample of an animal is described. Background Art

[0002] On animal farms, it is important to keep the animals healthy in order to increase milk / meat production. For example, on dairy farms, it is very important to inseminate the animals at the optimal moment in order to successfully inseminate the cows. For efficiency reasons, it is important to find the right time to inseminate each individual animal on the farm. In the event that an animal is not successfully inseminated, milk production will be affected.

[0003] Several biomarker measurements can be made on animals, such as measuring the levels of progesterone, LDH (lactate dehydrogenase), BHB (beta-hydroxybutyrate) and urea. This can yield important information about, for example, estrus detection and / or pregnancy (based on measured progesterone levels) as well as mastitis (based on LDH) and ketosis (based on BHB) in individual animals. In addition, energy balance can be estimated (based on urea).

[0004] The milk analysis device / service module may be arranged to cooperate with the milk extraction apparatus in order to analyse milk samples of the animal, for example at a milking session or periodically before and after a milking session. The milk analysis device / service module may extract the milk sample and provide the milk sample on a lateral flow stick / lateral flow test strip / dry stick or the like. The milk may be diluted with a diluent which may also be used to flush the tube between test sessions. The diluent may be provided in a liquid container.

[0005] The lateral flow sticks may be held in a cassette, for example on a strip in a cassette as disclosed in document WO 2018236271. Thus, the milk analysis units may be easily managed on the farm by advancing one lateral flow stick at a time. Typically one lateral flow stick may be used per test sample. The cassette may comprise a large number of lateral flow sticks, however when all lateral flow sticks have been consumed the cassette with the lateral flow sticks must be replaced with a new one.

[0006] Thus, the farmer / operator is provided with important information about each individual animal. Biomarkers such as progesterone can be measured in a highly automated manner for all individual animals on a farm.

[0007] However, a problem may arise where the farmer cannot be sure that the results of the lateral flow test are valid. For example, the lateral flow rod may be affected by moisture and / or high temperature storage. In the event that the lateral flow rod is defective for some reason, a positive test for low progesterone in the milk sample may not be obtained, resulting in the animal not being detected in estrus.

[0008] For these reasons, it would be advantageous to find a way to determine that a lateral flow rod is in good condition and / or that a lateral flow test performed on a lateral flow rod is valid and reliable, preferably without imposing additional workload on the farmer to determine validity. Summary of the invention

[0009] It is therefore an object of the present invention to address at least some of the above problems and to assist farmers in indicating the presence of progesterone in milk samples of animals in a lateral flow test and to determine the validity of the results of a lateral flow test.

[0010] According to a first aspect of the present invention, this object is achieved by a system for determining the validity of the results of a lateral flow test. The system comprises a lateral flow stick, which is arranged to indicate progesterone in a milk sample of an animal by a lateral flow test. The lateral flow stick comprises a sample pad, which is configured to receive the milk sample. In addition, the lateral flow stick comprises a conjugate pad, which comprises antibody-treated gold particles, and when the milk sample is absorbed from the sample pad, the antibody-treated gold particles are dispersed into the milk sample. In addition, the lateral flow stick also comprises a porous membrane, which is used to receive the capillary flow of the milk sample from the conjugate pad. The porous membrane comprises a test line treated with a progesterone reference, which binds to the antibody-treated gold particles of the milk sample and thereby causes the test line to change color when exposed to milk comprising a progesterone level below a threshold limit. The porous membrane also includes a control line treated with an antibody reference that binds to the antibody-treated gold particles of the milk sample regardless of the progesterone level in the milk and thereby causes the control line to change color when exposed to milk comprising antibody-treated gold particles. The system further includes a sensor configured to capture an image of the control line of the lateral flow stick when the porous membrane comprising the test line and the control line has absorbed a milk sample. In addition, the system also includes a control unit. The control unit is configured to obtain a reference color tone of the control line. The control unit is also configured to determine a current color tone of the control line based on the image captured by the sensor during the ongoing lateral flow test. In addition, the control unit is configured to compare the reference color tone of the control line with the current color tone of the control line. In addition, the control unit is configured to indicate the validity of the lateral flow test performed on the lateral flow stick based on the comparison performed.

[0011] The system is intended to operate autonomously in agricultural environments such as barns. The temperature in barns may become very high, for example in the summer, and the temperature regulating device in the barn (if any) may malfunction or be insufficient. High temperatures or otherwise inappropriate storage of the lateral flow stick may cause the antibody-treated gold particles of the binding pad to burn into the cellulose. The milk sample will then not release enough gold particles to obtain a reliable progesterone measurement in the test line. By obtaining a reference hue for the control line and comparing the current hue of the control line with the reference hue, aging or degradation of the lateral flow stick can be detected at an early stage. Thus, the reliability of the lateral flow test based on the lateral flow stick is increased.

[0012] In a first possible implementation of the system according to the first aspect, the control unit may be configured to generate an alarm upon detecting a hue difference between the reference hue of the control line and the current hue of the control line exceeding a threshold limit.

[0013] Thereby, the farmer can be warned to replace the lateral flow rod before it deteriorates so much as to affect the results of the lateral flow test.The farmer is relieved from the pressure of continuously checking the validity of the lateral flow rod.

[0014] In a second possible embodiment of the system according to the first aspect or according to its first embodiment, the control unit can be configured to disable the lateral flow rod comprising the control line when the hue difference exceeding a threshold limit is detected between the reference hue of the control line and the current hue of the control line.

[0015] By disabling the lateral flow stick when a hue difference exceeding the threshold limit is detected on the control line, it is determined that the lateral flow test is considered invalid when the lateral flow stick ages / degrades, resulting in higher validity and confidence in the biomarker test.

[0016] In a third possible embodiment of the system according to the first aspect or according to any previously disclosed embodiment thereof, the system may comprise a first wireless communication device. In those embodiments, the lateral flow stick may be held in a cartridge, the cartridge comprising a second wireless communication device and a memory device, the second wireless communication device being adapted to communicate wirelessly with the first wireless communication device. In addition, the included control unit may be configured to transmit, when the color tone difference is detected, a blocking flag prohibiting further use of the cartridge via the first wireless communication device and the second wireless communication device for storage in the memory device of the cartridge.

[0017] By storing the blocking flag in the memory of the cartridge, the lateral flow stick / cartridge cannot be used in performing other devices when any other device cannot indicate the validity of the lateral flow test.

[0018] In a fourth possible implementation of the system according to the first aspect or according to any previously disclosed embodiment thereof, said reference hue of said control line may be obtained by extracting a pre-stored reference hue sample from a memory device.

[0019] By determining the hue of the control line during a relatively early test and storing it, for example on the first lateral flow stick on a cartridge used for the first time, and then using it as a reference hue for subsequent tests, a reliable reference hue is obtained so that any very small degradation of the chemistry on the lateral flow stick over time can be detected and determined.

[0020] In a fifth possible embodiment of the system according to the first aspect or according to any previously disclosed embodiment thereof, said reference shade of said control line may be obtained by extracting from said memory device a representation such as a value or an image captured by said sensor during a previous milk analysis period representing said control line of said lateral flow rod.

[0021] By storing and retrieving the reference hue to and from the memory device, it is ensured that the control line hue is compared to the correct reference hue, thereby improving the reliability of the lateral flow test and the lateral flow stick.

[0022] In a sixth possible implementation of the system according to the first aspect or according to any previously disclosed embodiment thereof, said reference shade of said control line may be obtained by capturing an image of a reference line of said lateral flow rod.

[0023] By applying a reference line on the lateral flow stick during the manufacture of the lateral flow stick, images of the reference line, the control line and / or the test line can be captured and the corresponding tones compared. Thus, there is no need to determine a reference tone, store the reference tone in a memory and then retrieve the reference tone from the memory in order to make a comparison between the reference tone and the control line. Thus, it can be quickly and reliably determined whether the lateral flow stick / test is valid. In addition, no memory is required, which saves resources and eliminates any possible errors during memory reading.

[0024] In a seventh possible embodiment of the system according to the first aspect or according to any previously disclosed embodiment thereof, the lateral flow stick is configured to expose at least a portion of the control line on the porous membrane for direct visual contact with the sensor. The sensor may be arranged to make direct visual contact with at least a portion of the control line on the porous membrane of the lateral flow stick when capturing an image of the at least a portion of the control line so as to avoid optical distortion.

[0025] By peeling off or otherwise preventing a plastic cover or the like from covering the porous membrane, it is ensured that the image captured by the sensor is not distorted or otherwise rendered indistinguishable.

[0026] In an eighth possible embodiment of the system according to the first aspect or according to any previously disclosed embodiment thereof, the control line of the lateral flow stick may be arranged further away from the sample pad than the test line.

[0027] By placing the control line downstream relative to the test line, it is ensured that if the control line has changed color tone, the gold particles have passed the area of ​​the sample pad including the test line. The reliability of the lateral flow test is further improved.

[0028] Due to the described aspects, manual intervention, maintenance and work intensity of the farmer by determining the validity of the result of the lateral flow test is minimized or at least reduced.

[0029] Other advantages and additional novel features will become apparent from the detailed description that follows. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Embodiments of the present invention will now be described in further detail with reference to the accompanying drawings, in which:

[0031] Figure 1 An example of a device for measuring biomarker values ​​of a milk sample of an animal is presented.

[0032] Figure 2A A cartridge is shown inserted into a service module according to an embodiment.

[0033] Figure 2B A belt including lateral flow rods according to an embodiment is shown.

[0034] Figure 3A A lateral flow rod according to an embodiment is shown.

[0035] Figure 3B A lateral flow rod according to an embodiment is shown.

[0036] Figure 4AResults of lateral flow tests performed on lateral flow sticks according to the embodiments are presented.

[0037] Figure 4B Results of lateral flow tests performed on lateral flow sticks according to the embodiments are presented.

[0038] Figure 4C Results of lateral flow tests performed on lateral flow sticks according to the embodiments are presented.

[0039] Figure 4D Results of lateral flow tests performed on lateral flow sticks according to the embodiments are presented. DETAILED DESCRIPTION

[0040] The embodiments of the present invention described herein are defined as a system that can be put into practice in the embodiments described below. However, these embodiments can be illustrated and implemented in many different forms and are not limited to the examples set forth herein; on the contrary, illustrative examples of the embodiments are provided so that this disclosure will be thorough and complete.

[0041] Still other objects and features may become apparent from the following detailed description considered in conjunction with the accompanying drawings. It should be understood, however, that the drawings are designed for illustrative purposes only and not as a definition of the limitations of the embodiments disclosed herein, for which reference will be made to the appended claims. In addition, the drawings are not necessarily drawn to scale, and unless otherwise indicated, the drawings are intended only to conceptually illustrate the structures and processes described herein.

[0042] Figure 1 A scenario is shown with an animal 100, which may be included in a herd of dairy cows at a dairy farm, and a system 10 for determining the validity of the results of a lateral flow test.

[0043] "Animal" may be any type of domesticated female milk- and / or meat-producing mammal, such as cows, goats, sheep, horses, camels, primates, dairy buffalo, donkeys, yaks, and the like.

[0044] Milk from the animal 100 may be extracted by a milking device 110 , such as a milking robot, a rotary milking parlor, or other milking apparatus for an automatic or voluntary milking system, and provided to a service module 120 .

[0045] In some embodiments, the service module 120 may be releasably insertable into the milking device 110. Thus, there may be an interface between the milking device 110 and the service module 120 for providing milk and possibly electricity to the service module 120 via the milking device 110.

[0046] The service module 120 includes various electronics and devices, such as a camera, one or more pumps, a tube element for connecting to an interface of the milking device 110, a motor, a communication unit, and the like.

[0047] The cartridge 130 may be removably inserted into the service module 120. The cartridge 130 includes a strip having a lateral flow stick or a dry stick (lateral flow sticks may also be referred to as dry sticks) configured to indicate biomarker values ​​of a milk sample of the animal 100. In some embodiments, the cartridge 130 may be configured to be removably inserted into the service module 120 and held in place by a fastening member such as a snap lock, a magnet, a screw, etc., and the door of the service module 120 may be closed to enclose the cartridge 130 within the service module 120, thereby further securing the cartridge 130 in place.

[0048] Thus, a milk sample of the animal 100 can be extracted from the animal 100 by the milking device and provided to one of the lateral flow bars on the belt of the box 130 by the service module 120. The lateral flow bar can react to the presence and / or amount of one or more biomarkers, such as by changing color, hue, or intensity of color / hue. A camera in the service module 120 can capture an image through an opening in the box 130. The captured image of the lateral flow bar can then be analyzed by the control unit, and the presence and / or amount of the biomarker in the milk sample can be estimated based on the intensity of the color.

[0049] In various embodiments, the measured biomarker may be, for example, progesterone, glycoprotein, estrogen, and / or gonadotropin-releasing hormone or any other similar biomarker related to reproduction of the animal 100 .

[0050] Progesterone is a hormone that regulates several physiological functions of the animal 100. Progesterone can prepare the uterus for pregnancy, maintain pregnancy in the event of fertilization, and prevent the animal 100 from showing signs of continued estrus and ovulation during pregnancy. For example, progesterone levels can rise at the beginning of pregnancy and can remain at high levels throughout the pregnancy of the animal 100. Progesterone levels in milk samples can be used to monitor pregnancy, estrus cycles (estrus detection), and / or postpartum ovarian activity. For these reasons, it is interesting for farmers to detect and track progesterone levels of animals 100 at the farm.

[0051] However, in some embodiments, the biomarkers measured may include LDH (lactate dehydrogenase), BHB (beta-hydroxybutyrate), urea and / or somatic cell count; or other biomarkers related to the state of the animal 100. In some embodiments, multiple of the above listed biomarkers may be measured. Alternatively, in some embodiments, the farmer may order a cartridge 130 comprising a certain lateral flow stick on a belt configured to measure a biomarker or a set of biomarkers selected by the farmer; and / or different cartridges 130 comprising lateral flow sticks on a belt configured to measure different biomarkers or sets of biomarkers during different time periods of the year.

[0052] In some embodiments, the dosing module may also be removably insertable into the service module 120. The dosing module may include, for example, a needle and / or one or more pumps. A diluent container with a diluent may be located outside the dosing module.

[0053] Figure 1 and Figure 2A A general overview of the provided solution is depicted without going into too much detail in order to give the reader a rough overview. Figure 2B An example of details of the entities involved, specifically the box 130 and the belt, and how the box and the belt interact with each other and how the lateral flow rods can be arranged, is disclosed in . Figure 3A and Figure 3B Details of the lateral flow bars are depicted, and Figure 4A , 4B and 4C show examples of results of lateral flow tests performed on lateral flow sticks.

[0054] Figure 2A A service module 120, a cassette 130, and a dosing module, as well as a scenario of the system 10 according to an embodiment are shown. The service module 120 includes electronics and devices for determining biometric values ​​of a milk sample received from an animal 100, such as a sensor 210, such as a camera or video camera, a tube element 220 for connecting to a milking device, a motor, a communication unit 230, etc. In some embodiments, the dosing module may include one or more pumps configured to act on the tube element 220 for advancing the milk sample through the tube element 220.

[0055] In the illustrated embodiment, the dosing module may include a needle 350 for applying a milk sample through an opening in the cartridge 130 to the lateral flow bars 180a, 180b, 180c on the strip 170 in the cartridge 130. The sensor 210 may then align the needle 350 with the lateral flow bars 180a, 180b, 180c on the strip 170 of the cartridge 130.

[0056] The camera of the service module 120 can capture images of the lateral flow rods 180a, 180b, 180c of the carrier tape 170 through the opening, and based on these images, the box external motor can adjust the tape 170 relative to the needle 350 to position a new lateral flow rod 180a, 180b, 180c on which a new test is to be performed.

[0057] The communication unit 230 may communicate with the control unit 150 , the database 140 , and / or the output unit 160 through a wired or wireless communication interface.

[0058] In some embodiments, such a wireless communication interface may include or at least be inspired by wireless communication technology, such as Wi-Fi, 3GPP LTE, Bluetooth (BT), to name just a few possible examples of wireless communication.

[0059] The service module 120 may also include a first wireless communication device 240 configured to perform short-range wireless communication with a second wireless communication device 250 of the box 130. Short-range wireless communication may include near field communication (NFC), Bluetooth (BT), radio frequency identification (RFID), nano networks, etc. By enabling wireless communication, information may be exchanged between the service module 120 and the box 130. The control unit 150 may, for example, store certain data in a memory device 260 of the box 130.

[0060] The control unit 150 may include one or more processing circuit systems, which may include one or more examples of the following: for example, a central processing unit (CPU), a processor, a processing unit, an application-specific integrated circuit (ASIC), a microprocessor, a graphics processing unit (GPU), or other processing logic that can interpret and execute instructions. Therefore, the expression "processing circuit system" used herein may refer to a processing circuit system including multiple processing circuits, such as any, some, or all of the processing circuits listed above.

[0061] The sensor 210 of the service module 120 is configured to check a lateral flow bar 180a, 180b, 180c on the belt 170 of the box 130 through the opening of the box 130. The sensor 210 can also help align the needle 350 and the position of the lateral flow bar 180a, 180b, 180c on the belt 170 by adjusting the belt 170 by the reels 131, 132 of the box 130.

[0062] Furthermore, the service module 120 further comprises a tube element 220 configured to receive a milk sample of the animal 100 through the milking apparatus and to provide the milk sample to a needle 350, ie a needle 350 comprised in the dosing module.

[0063] In some embodiments, the dosing module may additionally comprise at least one pump configured to act on the tube element 220 to provide the milk sample to the needle 350. The pump may thus act on the tube element 220 to propagate the milk sample through the tube element 220 to the needle 350 or to a mixing chamber of the needle 350. The mixing chamber may alternatively be located outside the needle 350.

[0064] The dosing module may also include a liquid ejector or drain 195 that can collect liquid that has been output by the needle 350. In some embodiments, when only milk is included, the liquid can be returned to the milk production line. In other embodiments, when the milk has been mixed with a diluent, the liquid can be transported away from the box 130 so as not to soak or contaminate other unused lateral flow rods 180a, 180b, 180c of the belt 170 on the box 130.

[0065] Control unit 150 is configured to determine a biomarker value, such as progesterone, of a milk sample of animal 100 based on analysis of images captured by sensor 210. In some embodiments, control unit 150 may be included in service module 120 or located external to service module 120.

[0066] The database 140 may store measured biometric values ​​of the animal 100 in association with an identification reference of the animal 100, a timestamp of the measurements and / or a reference color tone of the control line of the lateral flow sticks 180a, 180b, 180c. Other measurements and / or data related to the animal 100 may also be stored in the database 140, such as milk production, activity, breed, parity, rumination, lactation, rest, feed intake, energy balance, days in milk, milk production, age and possibly other similar animal status related parameters measured, for example, by a milk flow meter.

[0067] Output unit 160 may be, for example, a cellular mobile phone, a fixed or portable computing device, a computer tablet, a display, a pair of smart glasses, smart contact lenses, an augmented reality device, a smart watch, or a similar device with a user interface and wireless communication capabilities.

[0068] The farmer has access to a portion of the results of the biomarker measurements of the milk sample via the output unit 160. The farmer is thereby able to analyse the status of the animal 100, for example when to measure the progesterone level if / when the animal 100 is in estrus.

[0069] When a deviation exceeding a first threshold limit is detected between the result of the biomarker measurement and the corresponding reference value, an alarm may be output to the farmer. The alarm may include, for example, visual information, an audio message, a tactile signal, or a combination thereof, prompting the farmer to further investigate the cause of the detected result deviation. In some embodiments, in the case where multiple people are working with the herd, a broadcast may be made to multiple farmers and their corresponding associated output units 160.

[0070] Figure 2B A belt 170 is shown according to an embodiment. The cassette 130, which may be releasably inserted into the service module 120, comprises a belt 170, which in turn comprises a plurality of lateral flow bars 180a, 180b, 180c.

[0071] The lateral flow bars 180a, 180b, 180c may be arranged at an inclination angle α relative to an axis 197 orthogonal to the longitudinal axis 196 of the belt 170. In some embodiments, the inclination angle α may be, for example, 15 degrees or about 15 degrees or, for example, 10-30 degrees.

[0072] The openings 190a, 190b, 190c may be arranged between at least some of the lateral flow bars 180a, 180b, 180c, on the belt 170 or on the bottom film of the belt 170, i.e. between the welds 181a, 181b, 181c of at least some of the lateral flow bars 180a, 180b, 180c on the bottom film. The openings 190a, 190b, 190c are configured to allow liquid to be transported away from the lateral flow bars 180a, 180b, 180c during cleaning or before applying a milk sample to the lateral flow bars 180a, 180b, 180c.

[0073] The milk of the first animal 100 may contaminate the milk sample of another subsequently tested animal. To avoid contamination or carryover, the tube and needle 350 may be flushed with milk from the animal 100 to be tested before the milk sample is applied to the lateral flow rods 180a, 180b, 180c. To avoid flushed milk from the animal 100 to be tested from soaking and / or contaminating other unused lateral flow rods 180a, 180b, 180c, flushing may be performed through the openings 190a, 190b, 190c of the belt 170, for example by lowering the needle 350 through the openings 190a, 190b, 190c, and catching the flushed milk with the liquid ejector 195. The liquid ejector 195 may then transport the liquid out of the box 130 through the tube.

[0074] The belt 170 or the bottom film of the belt 170 may further include reference marks 185a, 185b, 185c configured to help the camera find the lateral flow rods 180a, 180b, 180c. The reference marks 185a, 185b, 185c may include, for example, holes, color markings, bar codes, simple geometric shapes, or the like.

[0075] Reference marks 185a, 185b, 185c can also help the camera determine the advancement of the top film sheet reel to peel off the top film of the lateral flow rods 180a, 180b, 180c enough to enable the milk sample to be applied to the lateral flow rods 180a, 180b, 180c without peeling off the top film of the next lateral flow rod 180a, 180b, 180c.

[0076] In addition, the belt 170 or the bottom film of the belt 170 may include a first group 173 of forward holes 175, which are arranged at the first edge 171 of the belt 170; and a second group 174 of forward holes 175, which are arranged at the second edge 172 of the belt 170 or the bottom film of the belt 170.

[0077] Each transverse flow rod 180a, 180b, 180c can be arranged individually on the belt 170 or the bottom film of the belt 170 through a weld 181a, 181b, 181c, and the sealed transverse flow rods 180a, 180b, 180c are arranged at a certain distance from each other.

[0078] Figure 3A and Figure 3B A cross section of a lateral flow rod 180a, 180b, 180c in an embodiment is shown. The lateral flow rod 180a, 180b, 180c is arranged to indicate at least one biomarker value of a milk sample of the animal 100 by a lateral flow test (which may also be referred to as a lateral flow immunochromatographic assay).

[0079] The lateral flow rod 180a, 180b, 180c includes a sample pad 310 configured to receive a milk sample from a needle 350. Milk, or a liquid mixture between milk and a diluent, can be applied to the sample pad 310. The sample pad 310 can include a porous structure for enabling capillary flow of the milk sample through the lateral flow rod 180a, 180b, 180c. The sample pad 310 can include or be made of cellulose fibers and / or woven meshes.

[0080] In addition, the lateral flow rods 180 a , 180 b , 180 c include a conjugate pad 315 including antibody-treated gold particles, and when the milk sample is absorbed from the sample pad 310 , the antibody-treated gold particles are dispersed into the milk sample.

[0081] Gold particles treated with antibodies will react with progesterone in the applied milk sample. Generally, gold nanoparticles, colored or fluorescent latex beads dried onto a conjugate pad may be used as labeling agents, resulting in high levels of variation due to instability and inconsistent release, according to some embodiments.

[0082] The gold particles are embedded in a conjugate pad 315, which may include a glass fiber portion located at the upper portion of the lateral flow rods 180a, 180b, 180c. Alternatively, the conjugate pad 315 may include cellulose and / or surface-modified polyester. When a milk sample is supplied to the upper end of the lateral flow rods 180a, 180b, 180c, the milk will be drawn from the upper portion of the rods 180a, 180b, 180c to the lower portion with the help of capillary forces.

[0083] The lateral flow stick 180a , 180b , 180c further comprises a porous membrane 320 for receiving the capillary flow of the milk sample from the conjugate pad 315 / sample pad 310 .

[0084] In different embodiments, the porous membrane 320 can include nitrocellulose membrane, cellulose, glass fiber, polyester, rayon, polymer, glass fiber, woven fiber, non-woven fiber, chromatographic gel membrane, diatomaceous earth, silica gel, silicon oxide, diatomaceous earth or other filter membrane. The porous membrane 320 can be designed to improve the capillary pumping speed of liquid through the lateral flow rod 180a, 180b, 180c. The porous membrane 320 includes a test line 360 ​​and a control line 370.

[0085] The test line 360 ​​is treated with a progesterone reference that binds to the antibody-treated gold particles of the milk sample and thereby causes the test line 360 ​​to change color when exposed to milk comprising progesterone levels below a threshold limit. Thus, when the milk has no progesterone levels or has low progesterone levels, the test line 360 ​​changes color to red / reddish. If / when the animal 100 is in estrus, the progesterone level in the milk sample is close to zero. This color change can then be detected by the sensor 210 and can be reported to the farmer and / or stored in the database 140 associated with the identity and / or time reference of the animal 100. This can also trigger insemination of the animal 100.

[0086] The control line 370 of the porous membrane 320 is treated with an antibody reference that binds to the antibody-treated gold particles of the milk sample regardless of the progesterone level in the milk and thereby causes the control line 370 to change color when exposed to milk including antibody-treated gold particles.

[0087] Therefore, in the event that the antibody-treated gold particles included in the conjugate pad 315 react with heat, moisture, etc., the control line 370 will not change color tone due to improper storage of the lateral flow rods 180a, 180b, 180c. The function of the lateral flow rods 180a, 180b, 180c may thereby be compromised, and since the lateral flow test is performed autonomously, it is important to detect a faulty lateral flow rod 180a, 180b, 180c and disregard any test performed on it; and preferably replace the faulty lateral flow rod with a functional lateral flow rod 180a, 180b, 180c before performing the next lateral flow test (or alert the farmer to replace the faulty lateral flow rod).

[0088] At the bottom of the lateral flow bars 180a, 180b, 180c, there may be disposed an absorbent pad 330. The absorbent pad 330 may include an absorbent configured to absorb excess milk from the porous membrane 320. The absorbent pad 330 may also include a porous desiccant configured to absorb moisture from ambient air.

[0089] During transport or handling, moisture in the air may influence the results of the biomarker tests, ie results different from the true value may be produced by the test, leading to erroneous conclusions about the milk sample.

[0090] The biomarker value / progesterone level of the received milk sample may be determined by taking an image of the test line 360 ​​by a sensor 210 such as a camera or video camera, and when the porous membrane 320 has absorbed the milk sample, the validity of the lateral flow test / lateral flow stick 180a, 180b, 180c may be determined by capturing an image of the control line 370. The control unit 150 may then obtain a reference hue for the control line 370 and compare the reference hue with the current hue of the control line 370 as determined by the sensor 210 and indicate the validity of the lateral flow test performed on the lateral flow stick 180a, 180b, 180c based on the comparison performed.

[0091] In some embodiments, the lateral flow bars 180a, 180b, 180c can be individually sealed on the band 170 by the welds 181a, 181b, 181c. Thus, the lateral flow bars 180a, 180b, 180c can be protected from liquid and moisture, which may affect the biomarker measurement. However, in the case of a broken seal, the optional desiccant of the absorbent pad can be used for the purpose of absorbing moisture from the ambient air. Thus, a more reliable result of the biomarker measurement is obtained.

[0092] In some embodiments, the absorbent of the absorbent pad 330 may include cellulose fibers impregnated with a porous desiccant. The porous desiccant of the absorbent pad 330 may include, for example, silica gel, activated clay, and / or molecular sieves.

[0093] In some embodiments, the absorbent pad 330 may include a sheet of paper that has been treated with silica gel. Thus, the desiccant paper of the absorbent pad 330 may provide high capacity adsorption within a semi-rigid structure. Millions of adsorbent particles may be included in a semi-rigid cellulose fiber matrix, which enables rapid drying and extraordinary design versatility.

[0094] Silica gel is an otherwise inert, non-toxic, water-insoluble white solid that may be applied to absorbent pad 330. However, other alternative embodiments may include desiccants including activated carbon, calcium sulfate, calcium chloride, and molecular sieves, such as zeolites.

[0095] Furthermore, the lateral flow rods 180a, 180b, 180c may include a supporting layer 340 on which the sample pad 310, the porous membrane 320, and the absorption pad 330 are arranged.

[0096] In addition, the lateral flow bars 180a, 180b, 180c can be individually packaged on the carrier tape 170. The individually packaged lateral flow bars 180a, 180b, 180c can be sealed by welds 181a, 181b, 181c, and wherein the sealed lateral flow bars 180a, 180b, 180c can be arranged at a distance from any other lateral flow bars 180a, 180b, 180c.

[0097] Figure 4A A lateral flow stick 180a, 180b, 180c is shown on which a lateral flow test has been performed. Both the test line 360 ​​and the control line 370 have changed in color to red / reddish.

[0098] The control unit 150 obtains a reference color tone 380 of the control line 370 , for example from the local memory 140 or a memory device of the cartridge 130 .

[0099] Thus, the control unit 150 determines the current hue of the control line 370 based on the images captured by the sensor 210 during the ongoing lateral flow test. The reference hue 380 is then compared to the current hue of the control line 370. The validity of the lateral flow test performed on the lateral flow sticks 180a, 180b, 180c is then indicated based on the comparison performed.

[0100] In the event that the hue difference between the reference hue 380 and the current hue of the control line 370 exceeds a threshold limit, the lateral flow test is considered invalid. In some embodiments, an alarm may be generated to warn the farmer and prompt the farmer to replace the lateral flow rods 180a, 180b, 180c.

[0101] In such Figure 4A In the test results shown, the colors of both the test line 360 ​​and the control line 370 have changed to red. The color difference between the reference color 380 and the color of the control line 370 is less than the threshold limit. Thus, the lateral flow rods 180a, 180b, 180c are in proper conditions, and the lateral flow test is considered to be valid and reliable.

[0102] In some embodiments, the control line 370 of the lateral flow stick 180a, 180b, 180c may be arranged further away from the sample pad 310 than the test line 360. This ensures that, if the control line 370 has changed color, this means that there are enough gold particles that have passed through the test line 360 ​​of the porous membrane 320 to potentially change the color tone.

[0103] Since the color of the test line 360 ​​has also changed to red, this indicates that the milk of the animal 100 does not include a progesterone level or includes a low progesterone level, ie, the progesterone level is below the threshold limit.

[0104] Low progesterone levels in the milk (i.e., below a predetermined or configurable threshold limit) in turn indicate that the animal 100 is in estrus, i.e., a stage of the oestrous cycle suitable for insemination. By correctly timing inseminations, herd-level fertility will be improved and repeat inseminations can be avoided, saving time for the farmer. Thus, when the test line 360 ​​has turned red / color, an alarm can be generated and sent to the farmer, prompting the farmer to inseminate a particular animal 100.

[0105] For a cow, the estrus cycle is about 21 days, and estrus lasts about 6-18 hours. By performing a lateral flow test at each milking event of an animal 100 (animals 100 are typically milked 2-4 times a day), it is likely that every estrus period of all animals 100 at the farm will be detected. In some embodiments, by utilizing the knowledge that the estrus cycle is about 21 days, the start of the (last) estrus cycle of each animal 100 can be stored in a memory 140 associated with the identity reference of the animal 100, and a lateral flow test can be triggered, for example, 20 days after the last detected estrus of each particular animal 100 and repeated for a predetermined number of milking events until low progesterone is detected. In the case where the milk of an animal 100 has high progesterone at about 20-22 days from the last estrus, the animal 100 is likely to be pregnant, and any further lateral flow tests on the animal 100 until after calving may be redundant. Transverse flow rods 180a, 180b, 180c are thereby saved.

[0106] exist Figure 4B In the illustrated lateral flow bars 180a, 180b, 180c, the hue difference between the reference hue 380 and the hue of the control line 370 is less than the threshold limit. Thus, the lateral flow bars 180a, 180b, 180c are in proper conditions, and the lateral flow test is considered valid and reliable.

[0107] However, test line 360 ​​does not change any color at all, which indicates that the progesterone content in the milk of animal 100 is high, ie, above the threshold limit. There is no reason to attempt to inseminate animal 100, as she will not be able to accept insemination.

[0108] exist Figure 4C In the illustrated lateral flow bars 180a, 180b, 180c, the test line 360 ​​does not change any color at all, as shown in FIG. Figure 4B However, the hue of the control line 370 has neither changed nor become sufficiently similar / close to the hue of the reference hue 380. This can be found by comparing the reference hue 380 with the current hue of the control line 370.

[0109] In some embodiments, the reference hue 380 of the control line 370 may be obtained by extracting a pre-stored reference hue sample from the memory device 140 , 260 .

[0110] In still other embodiments, the reference hue 380 of the control line 370 may be obtained by extracting from the memory device 140, 260 a representation of the hue of the control line 370 of the lateral flow stick 180a, 180b, 180c captured by the sensor 210 during a previous milk analysis period. The reference hue 380 of the control line 370 may, for example, be determined and stored on a first one of the first lateral flow sticks 180a, 180b, 180c of the cassette 130 used for the first time or on a first one of a plurality of first times used.

[0111] The representation of the hue of the control line 370 may include, for example, a captured and stored image of the control line 370 stored in the memory device 140, 260, coordinates in an RGB color space, coordinates in a chromaticity space, correlated color temperature, hue, saturation, etc.

[0112] By determining the reference hue 380 at an early stage in the use of the cartridge 130, it is ensured that the chemistry of the lateral flow rods 180a, 180b, 180c has not been affected by high temperatures, aging, increased moisture or other similar causes.

[0113] Thereby, it may be indicated that the lateral flow test is invalid and cannot be trusted.An alarm may be generated and sent to the farmer to prompt the farmer to replace the lateral flow stick 180a, 180b, 180c and / or to redo the lateral flow test.

[0114] Figure 4D A lateral flow stick 180a, 180b, 180c is shown on which a lateral flow test has been performed. Both the test line 360 ​​and the control line 370 have changed in color to red / reddish.

[0115] In the illustrated embodiment, the lateral flow rods 180a, 180b, 180c include a reference line 390 that includes a reference hue 380. The reference hue 380 is physically applied to the lateral flow rods 180a, 180b, 180c or cartridge 130 during its production process.

[0116] Similar to the control line 370, the reference line 390 including the reference color tone 380 can be treated with an antibody reference that binds to the antibody-treated gold particles of the milk sample regardless of the progesterone level in the milk. However, the reference line 390 can be sprayed or otherwise treated with gold particles in the state of manufacture of the lateral flow rods 180a, 180b, 180c. The color of the reference line 390 is thereby changed to the reference color tone 380 and can be used as a reference indicator.

[0117] Thus, sensor 210 can capture images of both control line 370 and reference hue 380 on reference line 390 in one image. Reference line 390 can, for example, include a reference line parallel / adjacent to control line 370 for quick comparison between the hues of control line 370 and reference line 390.

[0118] An advantage of creating the reference line 390 including the reference hue 380 during manufacturing is that the reference hue 380 is set at a point in time that ensures that the temperature conditions are controlled and ideal. Thus, a reliable reference hue 380 is ensured.

[0119] The control unit 150 may be configured to generate an alarm when a hue difference exceeding a threshold limit is detected between the reference hue 380 of the control line 370 and the current hue of the control line 370 .

[0120] In some embodiments, the control unit 150 may be configured to disable the lateral flow bars 180a, 180b, 180c comprising the control line 370 when a hue difference exceeding a threshold limit is detected between a reference hue 380 of the control line 370 and a current hue of the control line 370.

[0121] In some embodiments, the system 10 may include a first wireless communication device 240. In at least some of those embodiments, the lateral flow bars 180a, 180b, 180c may be held in a cartridge 130, the cartridge including a second wireless communication device 250 and a memory device 260, the second wireless communication device being used to wirelessly communicate with the first wireless communication device 240. The control unit 150 may then be configured to transmit a blocking flag prohibiting further use of the cartridge 130 via the first wireless communication device 240 and the second wireless communication device 250 for storage in the memory device 260 of the cartridge 130 when the color difference is detected.

[0122] The lateral flow rods 180a, 180b, 180c may be configured to expose at least a portion of the control line 370 on the porous membrane 320 for direct visual contact with the sensor 210. The sensor 210 may in turn be arranged to make direct visual contact with at least a portion of the control line 370 on the porous membrane 320 of the lateral flow rods 180a, 180b, 180c when capturing an image of the at least a portion of the control line 370 so as to avoid optical distortion.

[0123] The belt 170 may include a bottom film 340 on which the lateral flow rods 180a, 180b, 180c are individually arranged. The carrier belt 170 may include a top film configured to cover the lateral flow rods 180a, 180b, 180c, to be arranged on the bottom film 340, and to be peeled off each individual lateral flow rod 180a, 180b, 180c before applying the milk sample to the lateral flow rods 180a, 180b, 180c.

[0124] The bottom film 340 of the carrier tape 170 may include a bottom layer, a middle layer, and a top layer. The top film of the carrier tape 170 may include a bottom layer, a middle layer, and a top layer. In some embodiments, the bottom layer and the top layer of the bottom film 340 and / or the top film may be made of plastic, and the middle layer may be made of aluminum.

[0125] The aluminum foil may act as a moisture barrier, thereby preventing liquid and moisture from reaching the lateral flow bars 180a, 180b, 180c, thereby keeping the lateral flow bars dry and unaffected by soaking.

[0126] The reason for applying the top film is that it is important that the milk from the first animal 100 does not soak the lateral flow sticks 180a, 180b, 180c on which the subsequent animal will be tested for biomarkers, because the milk from the first animal 100 may contaminate the lateral flow sticks 180a, 180b, 180c of the second animal. For this reason, in addition to ensuring direct visual contact between the sensor 210 and the control line 370 on the porous membrane 320, the cartridge 130 may further include a desealer configured to remove the sealing tape from the lateral flow sticks 180a, 180b, 180c when the lateral flow sticks 180a, 180b, 180c are adjusted into a position aligned with the needle 350. In some embodiments, the top film may be thinner than the bottom film 340, for example, 10%, 20%, 40%, etc. thinner.

[0127] The bottom film 340 may include a bottom layer, an intermediate layer, and a top layer. The bottom layer and the top layer may be made of plastics, such as polyethylene, polypropylene, polyamide, polyethylene terephthalate, polyethylene terephthalate polyester, polychlorotrifluoroethylene, polyvinylidene chloride, polypropylene, polyvinyl chloride, and / or polystyrene or similar materials, such as thermoplastic polyesters. Specifically, the top layer may be made of polyethylene.

[0128] The middle layer of the bottom film 340 may be made of aluminum or an aluminum-based alloy, and may have a thickness of, for example, between 9 μm and 25 μm.

[0129] The top film of belt 170 may include a bottom layer, an intermediate layer and a top layer. The bottom layer and the top layer may be made of plastic, such as polyethylene, polypropylene, polyamide, polyethylene terephthalate, polychlorotrifluoroethylene, polyvinylidene chloride, polypropylene, polyvinyl chloride and / or polystyrene or similar materials. In particular, the bottom layer may advantageously be made of polyethylene.

[0130] The layers of the bottom film 340 and the layers of the top film may be laminated separately.

[0131] The middle layer of the top film may be made of aluminum or an aluminum-based alloy and have a thickness of, for example, between 9 μm and 25 μm.

[0132] Using a thin (e.g., about 9 μm) aluminum foil layer for the middle layer of the bottom film 340 and / or the middle layer of the top film has the advantage of allowing more (longer) tape 170 on the reels 131, 132 of the box 130. A thin aluminum foil layer is also cheaper than using a thick (i.e., about 25 μm) aluminum foil. However, using a thicker aluminum foil for the middle layer makes the tape 170 less sensitive to mechanical damage. In some embodiments, a compromise can be to use a thick aluminum foil, such as, for example, about 15-25 μm, for the middle layer of the bottom film 340, and a thinner aluminum foil (e.g., about 9-15 μm) for the middle layer of the top film.

[0133] The lateral flow bars 180a, 180b, 180c can be held between the bottom film 340 and the top film and sealed individually. The individual sealing of each lateral flow bar 180a, 180b, 180c can be achieved by welding the top layer of the bottom film 340 to the bottom layer of the top film. Thus, when the lateral flow bars 180a, 180b, 180c are not further receiving milk samples from the needle 350, the lateral flow bars are well protected from milk stains or moisture that may affect the operation of the lateral flow bars 180a, 180b, 180c. To facilitate welding, the top layer of the bottom film 340 and / or the bottom layer of the top film can be made of polyethylene, because polyethylene is easy to weld.

[0134] The purpose of the intermediate layer is to provide firmness to the belt 170 while also allowing the belt 170 to be flexible enough to roll on the reels 131, 132 of the belt 170. To this end, the intermediate layer may advantageously be made of an aluminum foil; or a foil made of an aluminum alloy. The aluminum foil of the intermediate layer forms a reliable moisture barrier, thereby ensuring that the lateral flow bars 180a, 180b, 180c remain in a dry state until tested by applying a milk sample.

[0135] The purpose of the bottom layer of the bottom film 340 is to protect the middle layer from scratches and other undesirable mechanical impacts, because the middle layer (particularly when made of aluminum foil) is fragile and sensitive to scratches. The same is true for the top layer of the top film. The bottom layer of the bottom film 340 and the top layer of the top film can advantageously be made of plastic as described above. Plastic also has the advantage of low friction, which ensures smooth operation of the belt 170 when it is distributed between the reels 131, 132 of the belt 170. Plastic is also convenient for welding, so that each lateral flow rod 180a, 180b, 180c can be sealed individually.

[0136] like Figure 1 , Figure 2A , Figure 2B , Figure 3A , Figure 3B , Figure 4A , Figure 4B , Figure 4C and / or Figure 4D At least some of the presented embodiments or portions thereof may be advantageously combined with one another to achieve further benefits.

[0137] The terminology used in the description of the embodiments illustrated in the drawings is not intended to be limiting of the described lateral flow rods 180a, 180b, 180c. Various changes, substitutions and / or alterations may be made without departing from the embodiments of the present invention as defined by the appended claims.

[0138] As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items. The term "or" as used herein should be interpreted as a mathematical or, that is, as an inclusive disjunction; rather than as a mathematical exclusive or (XOR), unless otherwise explicitly stated. In addition, the singular forms "a", "an", and "the" should be interpreted as "at least one", and thus may also include multiple entities of the same kind, unless otherwise explicitly stated. It should be further understood that the terms "includes", "comprises", "including", and / or "comprising" specify the presence of stated features, actions, integers, steps, operations, elements, and / or components, but do not exclude the presence or addition of one or more other features, actions, integers, steps, operations, elements, components, and / or groups thereof. A single unit, such as a processor, can implement the functions of several items recited in the claims. The mere fact that certain measures or features are recited in mutually different dependent claims, are shown in different drawings or are discussed in connection with different embodiments does not indicate that a combination of these measures or features cannot be used to advantage. The computer program may be stored / distributed on a suitable medium, such as an optical storage medium or a solid-state medium provided together with or as part of other hardware, but may also be distributed in other forms, such as via the Internet or other wired or wireless communication systems.

Claims

1. A system (10) for determining the validity of a result of a lateral flow test, the system comprising: A lateral flow stick (180a, 180b, 180c) arranged to indicate progesterone in a milk sample of an animal (100) by a lateral flow test, the lateral flow stick (180a, 180b, 180c) comprising: a sample pad (310), the sample pad being configured to receive the milk sample; a conjugate pad (315), the conjugate pad comprising antibody-treated gold particles, the antibody-treated gold particles being dispersed into the milk sample when the milk sample is absorbed from the sample pad (310); a porous membrane (320) for receiving the capillary flow of the milk sample from the conjugate pad (315), wherein the porous membrane (320) comprises: a test line (360) treated with a progesterone reference that binds to the antibody-treated gold particles of the milk sample and thereby causes the test line (360) to change color when exposed to milk having a progesterone level below a threshold limit; and a control line (370) treated with an antibody reference that binds to the antibody-treated gold particles of the milk sample regardless of the progesterone level in the milk and thereby causes the control line (370) to change color when exposed to milk comprising antibody-treated gold particles; a sensor (210) configured to capture an image of the control line (370) of the lateral flow stick (180a, 180b, 180c) when the porous membrane (320) including the test line (360) and the control line (370) has absorbed a milk sample; and A control unit (150), the control unit being configured to: Obtaining a reference color tone (380) of the control line (370); determining a current hue of the control line (370) based on the image captured by the sensor (210) during the ongoing lateral flow test; comparing the reference hue (380) of the reference line (370) with the current hue of the reference line (370); and indicating the validity of the lateral flow test performed on the lateral flow stick (180a, 180b, 180c) based on the comparison performed, The reference color tone (380) of the control line (370) is obtained by extracting a pre-stored reference color tone sample from a memory device (140, 260).

2. The system (10) according to claim 1, wherein the control unit (150) is configured to generate an alarm when a hue difference exceeding a threshold limit is detected between the reference hue (380) of the control line (370) and the current hue of the control line (370).

3. A system (10) according to claim 1 or claim 2, wherein the control unit (150) is configured to disable the lateral flow rods (180a, 180b, 180c) including the control line (370) when a hue difference exceeding a threshold limit is detected between the reference hue (380) of the control line (370) and the current hue of the control line (370).

4. The system (10) according to claim 1 or 2, comprising: a first wireless communication device (240); and wherein the lateral flow rod (180a, 180b, 180c) is held in a box (130), the box comprising a second wireless communication device (250) and a memory device (260), the second wireless communication device being used for wireless communication with the first wireless communication device (240); and The control unit (150) is configured to: When a hue difference between the reference hue (380) of the control line (370) and the current hue of the control line (370) is detected to exceed a threshold limit, a blocking flag prohibiting further use of the box (130) is transmitted through the first wireless communication device (240) and the second wireless communication device (250) for storage in the memory device (260) of the box (130).

5. The system (10) according to any one of claims 1 to 2, wherein the reference color tone (380) of the control line (370) is obtained by extracting from the memory device (140, 260) a representation of the control line (370) of the lateral flow stick (180a, 180b, 180c) captured by the sensor (210) during a previous milk analysis period.

6. A system (10) according to any one of claims 1 to 2, wherein the reference color tone (380) of the control line (370) is obtained by capturing an image of a reference line (390) of the lateral flow rod (180a, 180b, 180c).

7. The system (10) according to any one of claims 1 to 2, wherein the lateral flow rod (180a, 180b, 180c) is configured to expose at least a portion of the control line (370) on the porous membrane (320) for direct visual contact with the sensor (210); and The sensor (210) is arranged to be in direct visual contact with at least a portion of the control line (370) on the porous membrane (320) of the lateral flow rod (180a, 180b, 180c) when capturing an image of the at least a portion of the control line (370) so as to avoid optical distortion.

8. The system (10) according to any one of claims 1 to 2, wherein the control line (370) of the lateral flow stick (180a, 180b, 180c) is arranged farther away from the sample pad (310) than the test line (360).

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