Methods and devices for measuring the levels of analytes in body fluids

Abstract

A method of testing for an analyte in an individual comprises providing colour information obtained from a digital image of a coloured reagent on an analyte test strip, the coloured reagent having been generated in accordance with analyte in a test sample, converting the colour information from the image into an analyte level, recording the analyte level in association with user-specific information (e.g. a QR code), repeating the above steps to obtain two or more records of analyte levels for the same user at different times and using the records to monitor personal health or to predict the likely development of a disease or condition or to diagnose a disease or condition or to monitor a treatment regime associated with variation in analyte levels in saliva.

Claims

1. A method of testing for an analyte in an individual, comprising: providing color information obtained from a digital image of a colored reagent on an analyte test strip, the colored reagent having been generated in accordance with analyte in a test sample; converting the color information from the digital image into an analyte level; recording the analyte level in association with user-specific information, wherein the digital image comprises user specific information; repeating the above steps to obtain two or more records of analyte levels for the same user at different times; and using the records to monitor personal health or to predict the likely development of a disease or condition or to diagnose a disease or condition or to monitor a treatment regime associated with variation in analyte levels in saliva; and further comprising a preliminary step of capturing the digital image of the colored reagent on the analyte test strip at a first site; and transmitting the digital image to a monitoring station at a second, remote site, where the color information from the image is converted into the analyte level.

2. The method according to claim 1, wherein the digital image comprises a color reference.

3. The method according to claim 1, wherein converting the color information from the digital image into an analyte level comprises: comparing color information from the digital image with color information obtained from images generated during a clinical trial, wherein the color information obtained from images generated during the clinical trial has been linked to levels of a given analyte.

4. The method according to claim 1, further comprising processing the digital image to obtain the color information from the digital image.

5. The method according to claim 1, further comprising determining the analyte level based upon luminance, saturation, or both luminance and saturation of the color.

6. The method according to claim 3, comprising using the comparison to identify incidence of high urate levels.

7. The method according to claim 1 is used for diagnosis of fetal stress.

8. The method according to claim 1 is used for diagnosis of risk of pre-eclampsia.

9. A method of testing for an analyte in an individual, comprising: (a) providing (i) a saliva sample from an individual in a pad of absorbent material, spaced from (ii) a test strip containing an indicator which is capable of generating a color change in accordance with the presence of an analyte; (b) bringing the pad into contact with the test strip and holding the pad in contact with the test strip for sufficient time for saliva in the pad to be combined with the indicator and generate a color in accordance with a level of an analyte if present; and (c) determining the level of analyte based upon the color change; wherein step (c) comprises transmitting information concerning the level of an analyte to a monitoring station at a remote site; and wherein the information transmitted comprises color information contained in or obtained from an image of the color on the test strip, and further comprising storing at least 5 test results for the same user taken at different times; and comparing these test results to monitor personal health or predict the likely development of a disease or condition or diagnose a disease or condition or to monitor a treatment regime associated with variation in analyte levels in saliva.

10. The method according to claim 9, wherein the indicator is capable of generating a color change in accordance with the concentration of an analyte.

11. The method according to claim 9, wherein the method comprises determining the analyte level based upon luminance, saturation, or both luminance and saturation of the color.

12. The method according to claim 9, comprising comparing test results to identify incidence of high urate levels.

13. The method according to claim 9, comprising carrying out the test using a device comprising: (a) a first arm, on which is mounted a pad of absorbent material; and (b) a second arm, comprising a test strip, wherein the test strip comprises a reagent portion comprising the indicator capable of generating a color change in accordance with the presence of an analyte; wherein the arms are connected by a hinge and can be pivoted on the hinge to bring the pad into contact with the reagent portion; and wherein the second arm additionally comprises a color calibration icon.

14. The method according to claim 13, wherein the second arm comprises a user identifier.

15. The method according to claim 9 is used for diagnosis of fetal stress.

16. The method according to claim 9 is used for diagnosis of pre-eclampsia.

Description

DESCRIPTION OF FIGURES

(1) The invention is now described in more detail with reference to specific embodiments and to the accompanying drawings, in which:—

(2) FIG. 1 is a schematic view of the front of a first device of the invention;

(3) FIG. 2 is a schematic view of the reverse of the device of FIG. 1;

(4) FIG. 3 is a schematic view of the side of the device of FIG. 1;

(5) FIG. 4 is a schematic view of the device of FIG. 1 in a closed position;

(6) FIG. 5 is a schematic, zoomed-in view of the interaction between the pad and the test strip when the device of FIG. 1 is in a closed position;

(7) FIG. 6 is a schematic view of the front of a second device of the invention;

(8) FIG. 7 is a schematic view of the device of FIG. 6 in a closed position;

(9) FIG. 8 is a schematic view of the reverse of the second arm of the device of FIG. 6 bearing the test strip;

(10) FIG. 9 is a schematic view of the first arm of a third device of the invention;

(11) FIG. 10 is a schematic view of the reverse of the second arm of the device of FIG. 9;

(12) FIG. 11 is a decision tree showing the steps involved in the digital image capture and transmission process i.e. the steps completed by an app run on the smartphone of a user; and

(13) FIG. 12 is a decision tree showing the steps involved in the processing of the digital image of the coloured reagent in the test strip.

(14) Referring to FIGS. 1-5, a first embodiment of a device for testing the levels of a given analyte present in saliva shown generally as 10 comprises two arms, a first arm 12 and a second arm 14, which are connected at one end via a hinge 15 which allows the two arms to be folded together. Rotation of each of the arms about the hinge is limited to 180°—a fully open, flat device is shown in FIGS. 1 and 2. The two arms are provided at the other end thereof with a clip or releasable lock arrangement, made up of loop 20 on the first arm and projection 21 on the second arm, by means of which the two arms can be locked together.

(15) In relation to the hinge, at the distal end of the first arm 12 is a pad of absorbent material (Capu-cell foam, 3 mm deep) 13 and at the distal end of the second arm 14 is a test strip 16. The area of the pad of absorbent material 13 is about 200 mm.sup.2 (20 mm×10 mm) and is larger than the area of the test strip 16, which is about 50 mm.sup.2 (10 mm×5 mm), to ensure that the entirety of the test strip 16 is contacted by the pad of absorbent material 13 when the two arms are bought together. Adjacent to the test strip 16 is a colour calibration icon 17. On the reverse side of the second arm 14 is a transparent window 18 through which both the test strip 16 and the colour calibration icon 17 are visible.

(16) During use of the device, a user places the pad in his/her mouth for a predetermined period (usually about 30 seconds) to soak the pad with saliva and then both the first arm 12 and the second arm 14 are rotated towards each other by pivoting on the hinge 15 such that the pad of absorbent material 13 makes contact with the test strip 16. Upon alignment of the first arm 12 with the second arm 14 the lock mechanism 20, 21 is engaged allowing the two arms to become locked together pressing the pad of absorbent material 13 onto the test strip 16. Through window 18, test strip 16 is visible and the colour change generated by the reaction of saliva with reagents in the strip can be seen, recorded and converted to a concentration.

(17) In FIG. 3 the side of the device is shown when the device is flat in an elongated open position. In this position, the depth of the pad of absorbent material 13 on the first arm 12 is shown and is about 3 mm, and can be compared to the depth of the test strip (drawings not to scale) 16 on the second arm 14, which is about 0.15 mm. The end of the hinge 15 which is approximately positioned in the middle of the device 10 is visible. The test strip 16 can be seen from the rear through the transparent window 18. Shown at opposing ends of the device are components of the lock mechanism, 20 on the first arm and 21 on the second arm.

(18) In FIG. 4 the device 10 is shown in a closed position. First arm 12 and second arm 14 are arranged in parallel such that the pad of absorbent material 13 on first arm 12 is in direct contact with the test strip 16 on the second arm 14. The lock mechanism of the first and second arm 20 and 21 respectively is engaged such that the arms remain locked together with the pad of absorbent material 13 pressed against the test strip 16.

(19) In FIG. 5 more detail of the interaction between the absorbent pad 13 on the first arm 12 and the test strip 16 on the second arm 14 can be seen. The absorbent pad 13 on the first arm 12 contacts the entirety of the test strip 16 on the second arm 14 and contacts a region of the face of the second arm surrounding the test strip. The colour calibration icon 17 can be seen on the second arm 14 adjacent to the test strip 16.

(20) Referring to FIGS. 6-8, a second embodiment of a device of the invention, shown generally as 100, comprises two asymmetrical arms, a first arm 112 and a second arm 114, which are connected at one end via a hinge 115 which allows the two arms to be folded together. Rotation of each of the arms about the hinge is limited to 180°—a fully open, flat device is shown in FIG. 6.

(21) In relation to the hinge, at the distal end of the first arm 112 is a pad of absorbent material (PureSorb™ Foam Wiper) 113 which has an area of about 200-300 mm.sup.2. In the middle of the second arm 114 is a shallow channel 116 for the test strip (not shown) containing the reagent portion. FIG. 8 shows the cassette 119 in which the test strip is comprised and illustrates how the test strip is attached to the reverse of the second arm i.e. by means of a clip. Adjacent to the shallow channel 116 in which the test strip resides is a colour calibration icon i.e. a CMYK icon 117 and a user-identifier i.e. a QR code 118. The area of the channel 116 is dictated by the size of the test strip, which is about 100 mm.sup.2 (10 mm×10 mm).

(22) During use of the device 100, a user places the pad 113 in his/her mouth for a predetermined period (usually about 30 seconds) to soak the pad with saliva and then both the first arm 112 and the second arm 114 are rotated towards each other by pivoting on the hinge 115 such that the pad of absorbent material 113 makes contact with the test strip. The two arms are held together by finger pressure for a predetermined period (say 3-5 seconds) before the device is opened by rotating the first arm 112 and the second arm 114 away from each other by pivoting on the hinge 115. In this position the test strip is visible and the colour change generated by the reaction of saliva with the reagents in the test strip can be seen, recorded and converted into a concentration.

(23) FIGS. 9-10 show two halves of a device comprising a third embodiment of the invention. The device comprises two asymmetrical arms, a first arm 127 (FIG. 9) and a second arm 129 (FIG. 10), which are connected at one end via a hinge 131 which allows the two arms to be folded together. FIG. 9 shows the front of the first arm 127 whereas FIG. 10 shows the reverse of the second arm 129.

(24) The first arm 127 contains a detachable head portion 133 and a stem portion 135. The head portion 133 comprises a pad of absorbent material (PureSorb™ Foam Wiper) 137 which has an area of about 200-300 mm.sup.2. The second arm 129 comprises a main body portion 139 and a releasable cassette 141 comprising a test strip 143. The test strip is accessible from the front surface of the second arm 129.

(25) During use of the device, a user attaches a new head portion 133 containing a pad of absorbent material to the stem portion 135 of the first arm 127. A new cassette 141 is also attached to the main body 139 of the second arm 129. At that point, a user places the pad 137 in his/her mouth for a pre-determined period (usually 30 seconds) to soak the pad with saliva and then both the first arm 127 and the second arm 129 are rotated towards each other by pivoting on the hinge 131 such that the pad of absorbent material 137 makes contact with the test strip. The two arms are held together by finger pressure for a predetermined period (e.g. 3-5 seconds) before the device is opened by rotating the first arm 127 and the second arm 129 away from each other by pivoting on the hinge 131. In this position the test strip is visible and the colour change generated by the reaction of saliva with the reagents in the strip can be seen, recorded and converted into a concentration.

(26) Digital Image Capture and Transmission

(27) FIG. 11 shows the design tree for an app run on the user's smartphone which controls digital image capture and transmission to the monitoring station.

(28) In the first step the user opens the app on her/his smartphone. The app then instructs the user to place the camera over the user-identifier (118 in FIG. 6), so that the inbuilt QR code reader within the app can read the QR code. If the QR code is suitably read then the user progresses to the next step. The user places the foam pad (labelled 113 in FIG. 6) in her/his mouth. Once the user has done so, the user starts the timer on the app which will tell the user when to remove the pad. Once the pad has been removed, the cover is removed from the test strip and the two arms of the device are rotated towards each other so that the pad comes into contact with the test strip. Once the pad is in contact with the test strip the user starts the timer on the app which tells the user when to re-open the device i.e. when to rotate the two arms of the device away from each other such that the test strip is visible. At that point, the app instructs the user to position the camera view over the test paper, the colour calibration icon and the user-identifier i.e. the QR code and take a photograph=digital image. Once the digital image is displayed, the app instructs the user to press send. Once the user presses send, the photograph=digital image showing the test strip, the colour calibration icon and the user-identifier, along with the date and time, is transmitted to a remote monitoring station where the colour information in the photograph is converted into an analyte concentration.

(29) Digital Image Processing and Conversion to Concentration

(30) FIG. 12 shows the steps involved in processing the digital image to convert the colour information contained within the test strip portion of the digital image into an analyte concentration. These steps are carried out at a remote monitoring station. Instep 1 the remote monitoring station receives the composite image comprising the reagent image data, the calibration data and the user identification details, associated also with a date and time stamp, from the user's smartphone. At this stage the user is identified only by means of the QR code, no personal information is transmitted. Thus the digital image is sent confidentially. In the second step the pre-processing of the digital image is to remove data noise. In the third step colour space feature extraction occurs. Various colour models can be used including HSV (Hue, Saturation, Value), L*A*B (Luminance (L) and two colour channels (a & b), YCbCr (Luma component (Y) and chrominance-blue (Cb) and chrominance red (Cr)) and CIE 1931. In the fourth step the result is plotted from the colour space feature extraction in a feature space plot already populated with data points indicating low, medium or high uric acid levels. The data points were obtained in a prior clinical trial and the low, medium, high categories agreed by a clinician. In the fifth step the k-nearest neighbors algorithm (k-NN) is used to classify the sample as high uric acid/medium uric acid or low uric acid. Once the sample has been classified, the result is stored alongside the user-identifier and the date and time. A trending algorithm monitors for instances of increased uric acid levels. Should an instance arise, the monitoring platform alerts the clinician who can link the user-identifier with a patient.

(31) Example 1

(32) Protocol: Monitoring of Salivary Urate and Use in Diagnosis

(33) The above described second embodiment of the device of the invention is used in combination with the above described app and monitoring station platform.

(34) Enrolment

(35) A pregnant woman enrolls into the monitoring and diagnosis programme. She is allocated unique identification details, encoded in a QR code that is attached to her notes at the hospital and to the device that she is given.

(36) Sample Taking

(37) The pregnant woman (referred to as the user) places the sponge-containing end of the device of FIGS. 6-8 into her mouth for approximately 30 seconds.

(38) The user then removes the sponge from her mouth, folds the device about the hinge and presses the sponge containing end, now wet with saliva, onto the test strip for approximately 3-5 seconds.

(39) Capture of Test Image and Calibration Image

(40) The user reopens the hinge after 3-5 seconds, revealing the test strip that has now to a greater or lesser extent reacted with urate in the saliva in the sponge, generating a colour change of the reagent in the test strip.

(41) Via an app run on the user's smartphone, the user takes a digital photograph (=digital image) of the test strip, including in the photograph the colour calibration icon and the QR code which are adjacent to the test strip. These provide colour calibration and patient identification details in the form of a number.

(42) The user transmits, by pressing send on the app, to a remote monitoring station the digital image comprising a digital image of the coloured reagent, a digital image of the colour calibration icon and a digital image of the QR code.

(43) Processing of Image Data

(44) The remote monitoring station receives the composite image comprising the reagent image data, the calibration data and the user identification details, associated also with a date and time stamp.

(45) If this is the first data received for that user, then a new set of records is generated.

(46) If there is an existing set of records for that user, then the data is added to the set.

(47) The image data is processed by colour space feature extraction and plotted on a feature space plot. A K-NN algorithm is then used to classify the colour content of the reagent image as “low”, “medium” or “high” uric acid level.

(48) If a user generates a single “high” reading, an alert is generated.

(49) If the “high” reading is generated after three or more “low” readings, then a “one-off” alert is generated.

(50) If the user generates a “high”, preceded by two or more “medium” readings in the previous three weeks, then a “trending high” alert is generated.

(51) The alert is transmitted to the hospital; only there can combining the QR code and hospital records identify the user who can be contacted by the appropriate staff member e.g. mid-wife, clinician etc.

(52) Reminders

(53) The user is sent a reminder to carry out another test once every week during the monitoring period.

(54) The monitoring period beings at week 20 of pregnancy and continues until term.

(55) Accordingly, the invention provides methods for testing for an analyte in an individual and devices for use therein.