TESTING SYSTEM ARRANGEMENT AND METHOD FOR TESTING

Abstract

This invention relates to a testing system arrangement for assessing the level of a biochemical marker, comprising a disposable device (2) with a sample inlet (4) and a at least one visible detection compartment (5A, 5B), for detection of said bio-chemical marker, a mobile unit (8) including a digital camera arranged to capture a digital picture (60) of said at least one visible detection compartment (5A, 5B), software run on a processor for analysing said picture (60) to assess said level and means arranged to present the result (70) of said assessment in a display (8A) of or connected to, said mobile unit (8), wherein said disposable device (2) is arranged with at least one reference surface (12) having a predetermined colour setting that is known to said software to enable exact assessment of the colour within said detection compartment (5A, 5B) by the use of said reference surface (12) within said digital picture as a basis reference.

Claims

1-19. (canceled)

20. A testing system for assessing a level of a biochemical marker in a sample, said system comprising: a mobile unit (8) comprising: a housing (104) having at least one support surface, the support surface having a plurality of reference areas thereon; an illumination device configured to optimally illuminate the at least one visible detection compartment (5A, 5B) for imaging of the sample; a memory containing data indicative of a colour of the plurality of reference areas on the at least one support surface; and a camera directed toward the at least one visible detection compartment and configured to capture one or more images of the at least one visible detection compartment; and a disposable device (2) positioned on the at least one support surface and comprising: a sample inlet (4) configured to receive there-through a receiving device containing the sample; at least one visible detection compartment (5A, 5B) connected to the sample inlet (4) and configured to provide visibility for detection of said biochemical marker in the sample; and a separation filter between said inlet and said visible detection compartment (5A, 5B), wherein: the mobile unit (8) further comprises a processor configured to execute a software program to: (i) calibrate the system by comparing a colour of the plurality of reference areas captured in the one or more images against the colour of the reference area contained in the memory, said comparison being configured for determining whether the illumination device is optimally illuminating the at least one visible detection compartment (5A, 5B); and (ii) following a successful calibration, determine, based at least upon a colour detected within the at least one visible detection compartment (5A, 5B) in the one or more images, the level of the biochemical marker in the sample; and a display (8A) configured to present a result (70) of the determined level of the biochemical marker in the sample.

21. The testing system of claim 20, wherein: the camera is a digital camera configured to capture a video sequence; the one more captured images are obtained, via the software program, from at least one discrete instance within the video sequence.

22. The testing system of claim 20, wherein: the camera is a digital camera configured to capture a sequence containing a plurality of images; the captured images are obtained, via the software program, from at least two discrete images within the plurality of images.

23. The testing system of claim 20, wherein the illumination device is an integrated component of the mobile unit.

24. The testing system of claim 20, wherein the illumination device comprises a set of lights positioned within the housing.

25. The testing system of claim 20, wherein the display is an integrated component of the mobile unit.

26. The testing system of claim 20, wherein: the disposable device further comprises a scannable code associated therewith; the processor is further configured to, prior to comparing the colour of the reference area captured in the one or more images against the colour of the reference area contained in the memory, determine, based in part upon the scannable code, a model of the disposable device captured in the one or more images; and the determination, based upon the comparison and the colour detected within the at least one visible detection compartment (5A, 5B) captured in the one or more images, is further based upon the determined model of the disposable device.

27. The testing system of claim 20, wherein said software program, via the one or more processors, is further configured to enable in situ capturing, processing, and display of the result (70).

28. The testing system of claim 20, wherein the system further comprises at least one control mechanism configured to manipulate positioning of the disposable device relative to the mobile unit so as to satisfy one or more predetermined conditions.

29. The testing system of claim 28, wherein the one or more predetermined conditions include at least one of an angle of the camera relative to the disposable device, a distance between the camera and the disposable device, or an illumination intensity of the disposable device.

30. The testing system of claim 20, wherein the at least one control mechanism is at least one of integral within the software program or a template (1) configured to interactively guide the user in connection with capturing of the one or more images.

31. The testing system of claim 20, wherein said at least one visible detection compartment (5A, 5B) contains a reagent composition configured to react with one or more of lactate dehydrogenase (LDH), bilirubin, or glucose, for direct detection of the colour of said biochemical marker.

32. Testing system, according to claim 31, wherein the colour determined via the LDH test is further converted to an RGB colour model so as to distinguish all LDH intervals relative to one another.

33. Method for assessing the level of a biochemical marker in a sample, said method comprising the steps of: providing a mobile unit (8) comprising: a housing having at least one support surface with a plurality of reference areas thereon; a camera; a processor; and a memory containing data indicative of a colour of the plurality of reference areas on the support surface; positioning a disposable device (2) on the at least one support surface, the disposable device comprising: a sample inlet (4) configured to receive there-through a receiving device containing the sample; at least one visible detection compartment (5A, 5B) connected to the sample inlet (4) and configured to provide visibility for detection of said biochemical marker in the sample; and a separation filter between said inlet and said visible detection compartment (5A, 5B); capturing, via the camera and an illumination device, one or more images of the at least one visible detection compartment, the camera being directed toward the at least one visible detection compartment, the illumination device being positioned to optimally illuminate the at least one visible detection compartment (5A, 5B) for imaging the sample; performing, via execution of a software program by the processor, a calibration by comparing a colour of the plurality of reference areas captured in the one or more images against the colour of the reference area contained in the memory, said comparison being configured for determining whether the illumination device is optimally illuminating the at least one visible detection compartment (5A, 5B); determining, following a successful calibration, via execution of the software program by the processor, and based upon a colour detected within the at least one visible detection compartment (5A, 5B) in the one or more images, the level of the biochemical marker in the sample; and presenting, via the processor and an associated display, a result of the determined level of the biochemical marker in the sample.

34. Method according to claim 33, wherein the method further comprises the step of separating the sample, via the separation filter, by either inducing a sub-pressure or by capillary means.

35. Method according to claim 33, wherein the result is presented within five minutes of placement of the sample within the at least one visible detection compartment (5A, 5B).

36. Method according to claim 33, wherein the result is presented within one minute of placement of the sample within the at least one visible detection compartment (5A, 5B).

37. Method according to claim 33, wherein: the disposable device further comprises a scannable code associated therewith; the processor is further configured to, prior to comparing the colour of the reference area captured in the one or more images against the colour of the reference area contained in the memory, determine, based in part upon the scannable code, a model of the disposable device captured in the one or more images; and the determination, based upon the comparison and the colour detected within the at least one visible detection compartment (5A, 5B) captured in the one or more images, is further based upon the determined model of the disposable device.

38. The method of claim 33, wherein at least one control mechanism is provided for manipulation of the positioning of the mobile unit relative to the disposable device so as to satisfy one or more predetermined conditions prior to capturing of the one or more images.

39. The method of claim 33, wherein: the camera is a digital camera configured to capture a video sequence; the one more captured images are obtained, via the software program, from at least one discrete instance within the video sequence.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0031] In the following the invention will be described in more detail with reference to the attached drawings, wherein:

[0032] FIG. 1A schematically shows a first system according to the invention,

[0033] FIG. 1B schematically shows a modified system according to the invention,

[0034] FIG. 2A shows a possible embodiment of a disposal testing device according to the invention, seen from above,

[0035] FIG. 2B shows a cross sectional view a long line II B-II B in FIG. 2A, and

[0036] FIG. 3 shows a further example of a disposable test device in accordance with the invention.

DETAILED DESCRIPTION OF VARIOUS EMBODIMENTS

[0037] In FIG. 1B there is schematically shown a testing system in accordance with the invention, wherein a mobile unit 8 with a digital camera, preferably a smart phone, e.g. an iPhone, is used to take a digital picture 60, of a test result presented in viewing area 10 of a disposable testing device 2. In its simplest form the user merely captures the digital picture of the diagnostic device 2 without any other accessories than the mobile unit 8.

[0038] In another embodiment, see FIG. 1A, there is used a different kind of template 1 in the form of a housing 104 with a first support surface 101 for the smart phone 8 and a second support surface 105 for the testing device 2.

[0039] The digital picture 60 captured by the mobile unit 8 is transmitted to a server 50 via any appropriate connection (depending on the place of the location), e.g. the internet 40. At the server 50 a specifically tailored software quickly runs a dedicated program to determine the outcome of the test and directly retransmits the result 70 to the mobile unit 8 where the test result is displayed on the display 8A of the mobile unit 8. Preferably the disposable testing device 2 is also equipped a unique code 13, e.g. printed, that is also captured in the picture, by means of which the software can determine what kind of testing device 2 the picture 60 relates to, and possibly also other desired aspects, e.g. stored in a memory connected to the server 50.

[0040] Alternatively, the mobile unit 8 may be equipped with its own processor/software to have also the analysis performed in situ. In that case the software may also contain control features that assists the user to capture the image of the testing device, in accordance with a predetermined manner, e.g. to get the right angle and distance. This may for example be achieved by means of a triggering function in the software, that automatically captures the picture 60 if certain parameters are fulfilled (e.g. distance, angle) or (possibly in combination with the latter) by means of a aiming device in the display, that guides the user to position the mobile unit 8 in a desired position for taking the picture.

[0041] As presented in FIG. 1B there is shown a further embodiment for an arrangement that may also be used to facilitate guidance for taking the picture 60, i.e. a relatively simple template 1, i.e. in connection with producing a digital picture 60 of a test result. The test result is presented in a viewing area of the disposable testing device 2. The template 1 is arranged with a marking 102 indicating a desired positioning of the disposable test device 2 on the template 1. In a preferred embodiment the template 1 has an outer configuration (or marked frame) 103 adapted to control a beneficial positioning of the mobile unit 8 during capturing of the picture. This may easily be achieved by designing the template with a frame 103 that correspond to the geometry of the camera display in the mobile unit 8, such that a desired/correct positioning (i.e. distance between the test device and camera lens) is achieved when the frame fits into the viewer of mobile unit 8. Thereby a kind of standardized illumination may be achieved when using the flash of the mobile unit 8. Hence a kind of standardized illumination may be obtained, by simply setting a desired frame for each kind of mobile unit, e.g. to provide more or less the same illumination by means of the built in flash of that mobile unit. Not merely, simply by controlling a desired distance, but also indeed assisting in controlling a desired direction of the flash, since the frame will also assist in positioning the mobile unit 8 in a desired angle/plane (e.g. parallelly) in relation to the plane of the template, which normally will be put on a horizontal surface. The template 1 (which preferably is made in a durable material, e.g. paper enclosed in plastic) may be equipped with a number of frames 103 (not shown) each one corresponding to a specific mobile unit 8, and may also be equipped with written instructions (e.g. on the back side)

[0042] As shown in FIG. 2A the disposal test device 2 is arranged with one or more reference areas 12 having a colour that is exactly known by the server 50, implying that even if the digital picture 60, that is transmitted to the server 50, would be somehow distorted the software within the server 50 will be able to determine any possible colour change by knowing exactly the actual colour of that reference area 12. In the preferred embodiment the reference colour within the reference area 12 is the very same as the colour of the body of the disposable testing device 2, e.g. white plastic. This brings about several advantages, firstly that there will be no extra cost for producing a reference area 12 and furthermore that even if the reference area is scratched the very same colour will still be maintained since the whole body has the very same colour. In a preferred embodiment a protection foil (not shown) is applied onto the top surface of the testing device 2, which foil safeguards that no deposits will be present on the reference area 12, if maintained on until making the test.

[0043] Moreover the reference area may be on the support, as long as it is captured in the same image as the test area.

[0044] Trials that have been performed indicate that in a digital picture 60 there is a good correlation between change of colour (due to different illumination) of the reference area 12, and the corresponding change of colour (of another kind/frequency) within a visible compartment 10, e.g. arranged with a transparent wall, or a wall interacting in the reaction, implying that correction/calibration is relatively easy to achieve by means of software, in accordance with the invention.

[0045] In FIGS. 2A-2B is presented an example of disposable device 2 according to the present invention with a sample inlet 4 in the form of a sample inlet connected to a chamber 6 adapted to receive a capillary device 7 containing a sample 9 arranged to be placed onto a receiving device, e.g. a plasma separation device 3. The sample inlet 4 is preferably surrounded by a funnel-like insertion pit for guiding a capillary sample collector 7 into chamber 6. Herein is further seen said optical viewing areas 10A-10C which allow for observing ongoing reaction inside detection compartments 5A-5B.

[0046] FIG. 2A is seen from a planar top-view, and FIG. 2B is a cross-view according to IIB in FIG. 2A. Herein device 2 is supplied with test blood 9 by means of a capillary device 7 being filled with the sample, e.g. a whole blood amounting to, e.g. about 50 L. Depending on the patient and/or on the particular design of device 2 (e.g. number of detecting compartments, size of the channels etc.) various amounts of blood sample are imaginable, and it is possible to use as little as 1 L, or as much as 100 L, a preferred amount being between 25-75 L.

[0047] In order to facilitate insertion of sample the area around sample inlet 4 is preferably pitted for guiding capillary device 7 into chamber 6. In FIG. 2A the capillary device 7 has already been inserted into a compartment 6 of the cartridge 2 to interface the blood sample 9 with the cartridge 2 and placing the blood sample 9 onto the filter 31 of the plasma separation device 3. Instead of a capillary device 7 it is conceivable to provide the sample 9 by means of a pipette releasing a drop of sample onto a marked area on the cartridge 2. A negative pressure is manually generated (or by means of a passive filter, or by means of capillary force) and plasma is urged through the filter 31 and into plasma collection chamber 32 wherefrom it proceeds through microfluidic channel 33 and is distributed into different detection compartments 5A-C. As is seen in FIG. 2B the testing system comprises optical viewing areas 10B in that at least the portions 10A-C of the disposable device 2 above each detection compartment 5B is transparent, meaning each detection compartment 5B is visible and can be observed during ongoing reaction.

[0048] Each detection compartment 5A-C, forms an encapsulated unit, which besides of enabling merely filtered fluid to enter, also provides the advantage that the volume of the biological sample that is put in contact with the reagent is known. As is evident for the skilled person this known input data (volume) may be of essence in determining the output and to optimize conditions. Furthermore, in connection with blood, it is known that the amount of plasma may vary a lot from individual to individual, i.e. even if the same volume of blood is applied at the inlet a big variation of filtered amount of plasma may be obtained. In the preferred embodiment the volume within a compartment 5A-C is in the range 0.1-15 l, more preferred 3-10 l, and most preferred 4-9 l.

[0049] The separation filter can be of different types, exemplified but not limited to, blood separation filters, filters for separation by size, filters for affinity, capture or binding of specific components in the fluid to be filtered. The filters may be made of natural or synthetic material, or a combination thereof, and be of symmetric or asymmetric type. The separation can be performed by inducing a subpressure or by capillary means.

[0050] Each detection compartment 5A-C is prepared with a reagent composition Y, preferably of different kind in each compartment, e.g. arranged to react with one of the following biochemical markers: Hb, LDH, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate, Creatinine Kinase (CK), Creatinine, Amylasis (PIA), C-reactive protein (CRP), Hydrogen ion concentration (pH), Albumin, K, Mg and Ca. Preferably each device 2 comprises at least two detection compartments 5A-B for detecting Hb and LDH respectively, and optionally one or more detection compartment for detection of one or more of AST, ALT, lactate, CK, Amylasis, K, Mg and Ca. It is to be understood that the examples mentioned above are by no means limiting to the basic principles of the invention.

[0051] Moreover another component Z may be added to the reagent composition or added to the test sample before it reaches the compartment, of at least one compartment 5A-C. This component Z (from now called the inhibitor) is added to the composition Y with the purpose to block the biochemical marker up to a certain concentration, e.g. the upper normal limit of a specific biochemical marker. The inhibitor Z works through binding to the active site of the molecule and thereby prevent that the blocked biochemical marker-molecule is participating in the reaction coupled to the colour-change. The benefits are twofold: Firstly, specific reactions developing a very intensive colour reaction could be suppressed to optimize the possibility to detect change in colour with eye or software. Secondly, the inhibitor Z will stabilize the reaction and therefore prolong the time frame between when the sample is applied to the reagents and when the results should be checked.

[0052] After a predetermined time-span (e.g. after the reaction may have been interrupted by a reaction stopper) any colour-shift is visually detected by the user of the testing system 1. The total time from applying the blood sample 9 in 2A to determine test result in 2C is less than 10 minutes, but preferably less than 5 minutes and more preferred within one minute.

[0053] FIG. 2A presents a planar view of the testing system after that a possible reaction has taken place within detection compartments 5A-C. In order to determine the level of biochemical markers the colour shift (if any) in each detection compartment 5A-C is compared to a standard reference interval which is preferably provided together with the testing system. According to one embodiment of the invention the area next to each detection compartment 5A-C is provided with a number of reference colours 11 whereby assessment of marker-level is easily performed. Here, detection compartment 5A is arranged to determine presence of Hb, and 5B-C are arranged to determine or estimate levels of any other biochemical marker. When using the test card solely on a biochemical marker with known cut off between normal and abnormal this cut off could be shown as a colour reference if the developed colour/s in the detection well/s is more intense than the colour reference the test is positive. The adding of an inhibitor will make it possible to take away all the colour if the biomarker of interest is low and only present a visual colour if the cut off (the amount of inhibitor) is exceeded. However when using the inhibitor for colour modification (e.g. to decrease the intensity of a colour in high concentrations of a biochemical marker) it could be used together with a colour reference. However, when the test card is used together with a soft ware device the colour references is not necessary due to the fact that the concentration of the biochemical marker will be presented as interval data or continuous values in the software.

[0054] For instance in FIG. 2A a situation is exemplified where no colour-shift has occurred in the compartment for Hb 5A, indicating that the test is valid. A reaction has occurred in compartment 5B, which colour-shift corresponds to one of given reference colours 11, whereas no notable reaction has occurred in compartments 5C. Preferably a user of a testing system 1 is instructed to react if colour-shift has resulted in a certain colour intensity. Such instructions may be marked in connection to the reference interval, for instance in the form of a symbol indicating the parts of reference interval representing risk of hypoxia.

[0055] In FIG. 2A the standard reference 11 for compartments 5B-C has three colour sections, however a person skilled in the art will understand that this is in no way limiting regarding the invention.

[0056] Yet another example of possible reference interval 11 is seen in FIG. 3 where a standard reference 11 has only two colour sections, meaning a reading will provide a user with a positive or a negative answer only. Such a design of a reference standard is suitable in medical situations where it is possible to present a concentration limit above which it is always required to take medical action, or in situations where a simple and fast reading is more important than a quantitatively precise measurement of the marker level.

[0057] Thanks to the use of an inhibitor Z it may be significantly easier to distinguish between different intervals, i.e. identify/determine a test result, than according to conventional methods.

[0058] Moreover the test can be of lateral flow type comprising antibodies or of type similar to urine dipsticks where the sample is not guided.

[0059] The skilled person realizes that a large variety of modifications may be performed without the use of inventive skill, departing from the description above, e.g. the use of glass or some other suitable material in place of plastic etc. For instance, instead of directly capturing one digital image, it is foreseen that instead a video may be recorded and that either the software within the mobile unit 8 (or within a server) analysis the colour by means of the plurality of images of the video, or that the software automatically chooses one of the images (fulfilling certain criteria) for performing the analysis. Furthermore it is within the scope of the present invention to use housing for capturing the digital picture 60, with a first support unit adapted to correctly position the disposable test device in a desired position within the housing, preferably at the bottom thereof, and at the opposite side of the housing, at the top thereof, a second supporting unit for correct positioning of the mobile unit, having its camera lens directed towards the testing device. The mobile unit may then be locked in its position within the second supporting unit, to eliminate possible theft and also to facilitate easy and quick use of the equipment without any need of adjustments. Moreover the housing may be arranged with an appropriate set of lights, to provide the disposable test device with an appropriate illumination at the time of taking the picture. Of course the lights may be omitted, to instead use the internal flash of the mobile unit.

[0060] Many modifications and other embodiments of the inventions set forth herein will come to mind to one skilled in the art to which these inventions pertain having the benefit of example it is evident for the skilled person that the disposable device 2 may have a sample inlet 4 adapted to receive a sample without the use of capillary device 7, e.g. to receive a drop of blood directly from a finger. Further, it is evident for the skilled person that also other fluids, dispersed stool, etc., may be used in connection with the invention. Moreover, it is foreseen that the inlet 4, as understood in connection with the invention may be in different forms, e.g. in the form of a discrete opening as presented in the figures, or in the form of a relatively large inlet surface, e.g. a soaking layer attached to the card. Therefore, it is to be understood that the inventions are not to be limited to the specific embodiments disclosed and that modifications and other embodiments are intended to be included within the scope of the appended claims.

[0061] Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation. For instance the mentioning of server shall not be construed in a limiting manner, but instead that the term server, as used in the context, refers to an arrangement wherein remotely positioned capacity (e.g. processing capacity, memory capacity, support capacity, etc.) is being used, i.e. encompassing any different kind of server-setups, e.g. server-client models, peer to peer models, etc., and/or combinations thereof. Moreover it is evident that the server functionality may also be used to link the result to the medical record of an individual patient, e.g. by applying a sticker containing a patient identifier on the disposable device 2, before capturing the image, to enable the software to also identify the patient. Further functionality within the server system may be used to achieve automatic reordering of disposables 2, when a certain number has been consumed, etc..