PORTABLE ANALYZER FOR AUTOMATICALLY PERFORMING IMMUNOASSAYS, AND FOR ANALYZING AND INTERPRETING THE RESULTS THEREOF

Abstract

The present invention provides an Analyzer adapted to receive an immunoassay cartridge comprising an imaging module including a two-dimensional light sensor and a plurality of light sources. The light sources and the two-dimensional light sensor are arranged such that the light sources are adapted to illuminate a result display section and a graphical code of the immunoassay cartridge and the two-dimensional light sensor is adapted to acquire images of both the graphical code and the result display section. The analyzer comprises an oscillator portion being adapted to cause the immunoassay cartridge to perform oscillations at a pre-set oscillation frequency. The analyzer comprises a processing section adapted to process an image of the graphical code acquired by the two-dimensional sensor to determine the pre-set oscillation frequency. The analyzer comprises a controller adapted to control the oscillator portion to cause the immunoassay cartridge to oscillate at the pre-set oscillation frequency.

Claims

1. Analyzer (100) adapted to interact with a corresponding immunoassay cartridge (200) for automatically performing an immunoassay and for automatically analyzing and interpreting results of the immunoassay, the analyzer (100) being adapted to at least partially receive the immunoassay cartridge (200); the analyzer (100) comprising an imaging module (300) including a two-dimensional light sensor (301) at least partially surrounded by a plurality of light sources (303), whereby the light sources (303) and the two-dimensional light sensor (301) are arranged such that when the immunoassay cartridge (200) is at least partially received by the analyzer (100), the light sources (303) are adapted to illuminate at least a result display section (213) and a graphical code (211) provided at the immunoassay cartridge (200), and the two-dimensional light sensor (301) is adapted to acquire images of both the graphical code (211) and the result display section (213); characterized in that the analyzer (100) further comprises a mechanical module comprising a plurality of actuators and an oscillator portion (407); whereby each of the actuators is adapted to interact with a corresponding portion of the immunoassay cartridge (200), when the immunoassay cartridge is at least partially received by the analyzer (100) for automatically performing an immunoassay; whereby the oscillator portion (407) is arranged such that when the immunoassay cartridge (200) is received by the analyzer (100), the oscillator portion (407) is in mechanical contact with the immunoassay cartridge (200), the oscillator portion (407) thereby being adapted to cause the immunoassay cartridge (200) to perform oscillations at a pre-set oscillation frequency; wherein the analyzer (100) further comprises a processing section adapted to process an image of the graphical code (211) acquired by the two-dimensional light sensor (301) to determine the pre-set oscillation frequency; and the analyzer (100) further comprises a controller connected to the processing section and to the oscillator portion (407), the controller being adapted to receive, from the processing section, the pre-set oscillation frequency, the controller further being adapted to control the oscillator portion (407) to cause the immunoassay cartridge (200) to oscillate at the pre-set oscillation frequency.

2. Analyzer (100) according to claim 1, characterized in that the oscillator portion (407) comprises a position detection sensor adapted to detect a position of the immunoassay cartridge (200) with respect to the analyzer, when the immunoassay cartridge (200) is received by the analyzer (100).

3. Analyzer (100) according to any one of claim 1 or 2, characterized in that the oscillator portion comprises an oscillator plate (407) and in that the analyzer (100) and the immunoassay cartridge (200) are provided such that when the immunoassay cartridge (200) is received by the analyzer (100), the immunoassay cartridge (200) is placed on the oscillator plate (407).

4. Analyzer (100) according to any one of the preceding claims, characterized in that the plurality of actuators comprises at least a first actuator (401, 403, 405), a second actuator (401, 403, 405) and a third actuator (401, 403, 405), each being arranged moveable such that when the immunoassay cartridge (200) is received by the analyzer (100), each of the actuators (401, 403, 405) is adapted to be moved from an initial position in a direction towards the immunoassay cartridge (200), whereby the controller is adapted to automatically control movement of each of the actuators, preferably in accordance with information received from the processing section and determined from processing an image of the graphical code (211) acquired by the two-dimensional light sensor (301).

5. Analyzer (100) according to claim 4, characterized in that the first actuator (401, 403, 405), the second actuator (401, 403, 405) and the third actuator (401, 403, 405) are linearly moveable in a direction essentially perpendicular to the oscillator plate and in that the analyzer (100) comprises at least one actuator position sensor, preferably a potentiometer, for a corresponding one of the actuators (401, 403, 405), which actuator position sensor is connected to the controller and is adapted to convert a position of the corresponding actuator (401, 403, 405) into a signal, preferably a voltage signal.

6. Analyzer (100) according to claim 5, characterized in that the controller is adapted to control the position of the corresponding actuator (401, 403, 405) by controlling a corresponding motor which is mechanically connected to the corresponding actuator (401, 403, 405) in response to the voltage signal.

7. Analyzer (100) according to any one of claims 5 to 6, characterized in that upon movement from the initial position towards the immunoassay cartridge (200), at least one of the actuators (401, 403, 405) is adapted to compress, preferably to perforate, a corresponding portion of the cartridge (200) upon engagement with the corresponding portion of the immunoassay cartridge (200).

8. Analyzer (100) according to any one of claims 5 to 7, characterized in that at least one of the actuators (401, 403, 405) is provided with a guiding portion (415), and in that upon movement from the initial position towards the immunoassay cartridge (200), the at least one actuator (401, 403, 405) is adapted to guide a sample collection member at least partially into an inner chamber of the immunoassay cartridge (200).

9. Analyzer (100) according to any one of claims 5 to 8, characterized in that at least one of the actuators (401, 403, 405) is provided with a contact portion and in that upon movement from the initial position towards the immunoassay cartridge (200) the contact portion of the at least one of the actuators (401, 403, 405) is adapted to come into contact with a corresponding portion of the immunoassay cartridge (200) to move a test strip at least partially into an inner chamber of the immunoassay cartridge (200).

10. Analyzer (100) according to any one of the preceding claims, characterized in that the analyzer (100) further comprises a printer, preferably a thermal printer, for automatically printing results of the immunoassay, a screen, preferably an LCD screen, for displaying results of the immunoassay and a storage for storing results of the immunoassay, and incorporates the imaging module (300), the oscillator portion (407), the processing section, the controller, the first actuator (401, 403, 405), the second actuator (401, 403, 405), the third actuator (401, 403, 405), the printer, the screen and the storage in a single portable device with a total weight of less than 10 kg, preferably of less than 7.5 kg, more preferably of less than 5 kg and most preferably of less than 2.5 kg.

11. Method for automatically performing an immunoassay using the analyzer (100) according to any one of claims 1 to 13 and a corresponding immunoassay cartridge (200), the method comprising the following steps, preferably in the given order: a step A of inserting a sample collection member comprising a sample to be analyzed by the immunoassay into a first position at least partially inside the immunoassay cartridge (200); a step B of inserting the immunoassay cartridge (200) at least partially into the analyzer (100); a step D1 of controlling a first actuator (401, 403, 405) to be moved from an initial position towards the immunoassay cartridge (200), thereby compressing a flexible portion of the immunoassay cartridge (200), thus introducing a dilution comprising a substance for analysis of the sample, preferably comprising a buffer for homogenizing reagents, preferably antibodies, into an inner chamber of the cartridge (200); a step E of controlling the oscillator portion (407) to cause the immunoassay cartridge (200) to perform first oscillations at a pre-set oscillation frequency; a step D2 of controlling a second actuator (401, 403, 405) to be moved from an initial position towards the immunoassay cartridge (200) into engagement with the sample collection member, thereby guiding the sample collection member including the sample to be analyzed at least partially into the inner chamber of the immunoassay cartridge (200) into contact with the dilution to form a mixture of sample and dilution; a step F of controlling the oscillator portion (407) to cause the immunoassay cartridge (200) to perform second oscillations at a, preferably the, pre-set oscillation frequency in order to homogenize the mixture of the dilution and the sample; a step G of controlling a third actuator (401, 403, 405) to be moved from an initial position towards the immunoassay cartridge (200), thereby moving at least one test strip at least partially into the inner chamber of the immunoassay cartridge (200) into contact with the mixture; a step H of waiting for a pre-set time to allow incubation of the test strip with the mixture; a step I of acquiring a result image of a result display section (213) of the immunoassay cartridge (200); and a step J of processing and analyzing the result image in order to determine as a result result-substances comprised by the sample, wherein steps D1 to J are performed automatically by the analyzer (100).

12. Method according to claim 11, further comprising a step C1 of acquiring an image of a graphical code (211) provided at the immunoassay cartridge (200); a step C2 of processing the image of the graphical code (211) in order to determine at least one of the pre-set oscillation frequency and/or the pre-set time, wherein steps C1 and C2 are performed in advance to step D1, and wherein steps C1 to J are performed automatically by the analyzer (100).

13. Method according to claim 12, wherein in step J, it is determined that a result-substance is present in the sample, when a detected signal corresponding to the result-substance is above an internal threshold; and wherein step C2 further comprises processing the image of the graphical code (211) in order to determine the pre-set internal threshold.

14. Method according to claim 13, wherein in step J, when it is determined that a result-substance is present in the sample, a positive result is output when a concentration of the result-substance in the sample derived from the detected signal is above a threshold concentration; and wherein step C2 further comprises processing the image of the graphical code (211) in order to determine the threshold concentration.

15. Immunoassay analysis system comprising the analyzer (100) according to any one of claims 1 to 10 and a corresponding immunoassay cartridge (200), preferably wherein the immunoassay cartridge comprises a holder and a cassette for housing an immunoassay strip.

16. Immunoassay analysis system comprising the analyzer (100) according to any one of claims 1 to 10 and a holder for a cassette comprising at least one immunoassay strip, wherein the graphical code is provided on a surface of the holder and wherein the graphical code encodes a pre-set internal threshold and a pre-set threshold concentration; whereby the analyzer (100) is adapted to automatically analyze a result of an immunoassay and determine that a result-substance is present in a sample when a detected signal corresponding to the result-substance is above the internal threshold; and wherein the analyzer is further adapted to output a positive result when a concentration of the result-substance in the sample derived from the detected signal is above the threshold concentration.

17. Analyzer (100) adapted to interact with a corresponding immunoassay cartridge (200) for automatically performing an immunoassay and for automatically analyzing and interpreting results of the immunoassay, the analyzer (100) being adapted to at least partially receive the immunoassay cartridge (200), the analyzer being adapted to perform the following steps, preferably in the given order: a step A of inserting a sample collection member comprising a sample to be analyzed by the immunoassay into a first position at least partially inside the immunoassay cartridge (200); a step B of inserting the immunoassay cartridge (200) at least partially into the analyzer (100); a step D1 of controlling a first actuator (401, 403, 403) to be moved from an initial position towards the immunoassay cartridge (200), thereby compressing a flexible portion of the immunoassay cartridge (200), thus introducing a dilution comprising a substance for analysis of the sample, preferably comprising a buffer for homogenizing reagents, preferably antibodies, into an inner chamber of the cartridge (200); a step E of controlling an oscillator portion (407) of the analyzer (100) to cause the immunoassay cartridge (200) to perform first oscillations at a pre-set oscillation frequency; a step D2 of controlling a second actuator (401, 403, 405) to be moved from an initial position towards the immunoassay cartridge (200) into engagement with the sample collection member, thereby guiding the sample collection member including the sample to be analyzed at least partially into the inner chamber of the immunoassay cartridge (200) into contact with the dilution to form a mixture of sample and dilution; a step F of controlling the oscillator portion (407) to cause the immunoassay cartridge (200) to perform second oscillations at a, preferably the, pre-set oscillation frequency in order to homogenize the mixture of the dilution and the sample; a step G of controlling a third actuator (401, 403, 405) to be moved from an initial position towards the immunoassay cartridge (200), thereby moving at least one test strip at least partially into the inner chamber of the immunoassay cartridge (200) into contact with the mixture; a step H of waiting for a pre-set time to allow incubation of the test strip with the mixture; a step I of acquiring a result image of a result display section (213) of the immunoassay cartridge (200); and a step J of processing and analyzing the result image in order to determine as a result result-substances comprised by the sample, wherein steps D1 to J are performed automatically by the analyzer (100).

18. Analyzer (100) according to claim 17, the analyzer (100) being the analyzer (100) according to any one of claims 1 to 11.

Description

4. DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0063] In the following, the invention is described exemplarily with reference to the enclosed figures in which:

[0064] FIG. 1 shows a schematic illustration of an analyzer 100 with a corresponding immunoassay cartridge 200 received by the analyzer;

[0065] FIG. 2 shows a schematic exploded view of the analyzer 100;

[0066] FIG. 3 shows a schematic illustration of a lateral flow strip;

[0067] FIG. 4 shows exemplarily examples of an immunoassay; and

[0068] FIGS. 5 and 6 show the results of FIG. 4 as corresponding curves.

[0069] FIG. 1 shows a schematic view of an analyzer 100. As illustrated in this schematic figure, the immunoassay cartridge 200, which is schematically shown by the dashed square, is received by the analyzer 100, i.e. is placed with respect to an imaging module 300 comprising a CMOS sensor 301 (alternatively, a CCD sensor may be used) such that a result display section 213 and a graphical code 211 (both only schematically shown) face the CMOS sensor 301. The dashed line schematically illustrates a holder for housing a cassette 205 which in turn houses a lateral flow strip 209 for performing the immunoassay. As mentioned above, while the cassette may be a commercially available, standardized component, the holder preferably is dedicatedly fabricated for the analyzer thus allowing for a particularly beneficial interaction between the analyzer and the cartridge comprising the holder and the cassette.

[0070] The result display section 213 may be an opening in an outer surface or an outer shell or wall of the immunoassay cartridge 200 which faces the CMOS sensor 301. This opening can be covered by a transparent material such as a transparent plastic sheet.

[0071] As illustrated in FIG. 1, the analyzer is provided with a mechanical module 400 which is provided with three schematically shown linear actuators 401, 403, 405. In the shown case where the immunoassay cartridge 200 is received by the analyzer 100, the immunoassay cartridge 200 is placed on an oscillator portion, e.g. an oscillator plate 407. As can be taken from this figure, the linear actuators 401, 403 and 405 are arranged movable in a direction essentially perpendicular to the orientation of the oscillator plate 407. As the skilled person will understand, upon a movement of the linear actuators 401 and 403 downwards in the figure, these actuators will engage corresponding portions 201, 203 of the immunoassay cartridge 200. For example, with reference to FIG. 2 it is shown that the actuator 405 is provided with a contact portion 406 at its end which is adapted to come into contact with a corresponding portion of the immunoassay cartridge 200 to move e.g. one or more test strips at least partially into an inner chamber of the immunoassay cartridge.

[0072] Turning back to FIG. 1, it can be seen that similarly, upon movement for example of the actuator 403 downwards in the figure, the portion 203 will be pressed and moved downwards in the figure further into an inner chamber (not visible in the figure) provided inside the portion 207. For example, the portion 203 can be a flexible portion of the immunoassay cartridge which becomes compressed due to the interaction with the linear actuator 403 whereby a dilution absorbed by the flexible portion is introduced into the inner chamber provided inside the portion 207 of the immunoassay cartridge 200.

[0073] Further, FIG. 1 shows the cassette 205 which houses a lateral flow strip 209 for performing the immunoassay which is shown in more detail in FIG. 3. As shown in FIG. 1, in order to assure an optimal illumination of the lateral flow strip 209, the optical module 300 is provided with a plurality of light sources 303 which in the shown embodiment are LEDs 303. It was found that optimal performance of the analyzer can be achieved by using white light LEDs 303 surrounding a CMOS or CCD sensor 301.

[0074] As further shown, the analyzer 100 can be operated using simple batteries 501 which contribute to the light weight construction of the analyzer as compared to power supplies as they are often necessary for large laboratory devices. It was found that using a battery 501 with a capacity 6000 mAh for an LCD screen which can be incorporated with the analyzer 100 and the electronics and using a 2000 mAh battery for a printer incorporated within the analyzer, a total weight of only about 2.4 kg can be achieved.

[0075] Further, schematically shown are an electrical network 503 which is used to connect the individual components with an electronic module 505, an output and documentation portion 507 and a personal computer 509. The electronic module 505 may include a processing section adapted to process an image of the graphical code 211 acquired by the two-dimensional sensor 301 to determine the pre-set oscillation, frequency. The electronic module 505 may further include a controller connected to the processing section and to the oscillator portion 207. The controller may thus be adapted to receive, from the processing section, the pre-set oscillation frequency and may be adapted to cause the immunoassay cartridge 200 to oscillate at the pre-set oscillation frequency.

[0076] For example, the CMOS sensor 301 can be connected to the electronic module 505 and adapted to read the graphical code 211 to determine a pre-set oscillation frequency. The oscillator plate 407 can be connected to the electronic module 505 and the controller provided within the electronic module 505 is adapted to control oscillation of the oscillator plate 407 at the pre-set oscillation frequency determined by the electronic module through processing of the image of the graphical code 211 acquired by the CMOS sensor 301.

[0077] The electronic module 505 may further include a CPU connected to the controller and storage means. The storage means may be used for saving an algorithm run using the CPU to cause the analyzer 100 to perform actions necessary for performing an immunoassay in connection with the immunoassay cartridge 200 in an automated manner. At the same time, the algorithm may include steps for processing result images of the immunoassay acquired using the optical module 300. Thus, the analyzer 100 according to the present invention allows for performing an immunoassay, acquiring result images of the immunoassay and processing the same in a fully automated manner making use of a small, lightweight modular device which can e.g. easily be transported in a police car.

[0078] Further, the analyzer 100 is provided with an output and documentation portion 507 including for example a thermal printer which can automatically print the results of an immunoassay. Further, the output and documentation portion 507 can include an LCD screen for displaying the results of the immunoassay and the output and documentation portion 507 can be connected to a personal computer for saving results of the immunoassay.

[0079] FIG. 2 shows a schematic exploded view of the analyzer 100. As shown in this exploded view, the linear actuators 401, 403 and 405 extend from respective base portions 411 (only one indicated in the figure) in directions essentially parallel to a plane of the oscillator plate 407. As shown, the base portions 411 travel along respective guide rails 413 when the actuators 401, 403, 405 move from the initial position as shown in FIG. 2 towards the immunoassay cartridge (not shown in the figure), i.e. downwards in FIG. 2. In a preferred embodiment, two guide rails are provided for each actuator. As may be taken from FIG. 2, by the advantageous provision of two guide rails 413 for each linear actuator a particularly controlled and stable linear movement of the linear actuators in a direction essentially perpendicular to the oscillator plate is assured.

[0080] As shown in FIG. 2, the actuator 401 is provided with a guiding portion 415 extending in a direction essentially perpendicular to the plane of the oscillator plate 407. This guiding portion 415 is adapted to receive a portion of a sample collection member (not shown in the figure) such as a stick connected to an absorbing portion for absorbing a sample for carrying out the immunoassay. As can be taken from the figure, the guiding portion preferably is an essentially cylindrically shaped member adapted to receive a linear portion, i.e. a stick-like portion, of the sample collection member. Thus, a particularly stable and controlled guidance may be achieved.

[0081] Further, FIG. 2 illustrates the optical module 300 exemplarily showing LEDs 301 (only one indicated in the figure) which surround a CMOS or CCD sensor 301 provided in the center. The optical module 300 is provided fixedly attached to a support structure 317 which extends from a supporting plate 319 in a direction essentially perpendicular to the orientation of the oscillator plate 407. As shown also in the figure, the support plate 319 also supports holding portions 417 (only one indicated in the figure) which hold the oscillator portion 407 in a manner that an oscillation is controlled to be in a plane perpendicular to the movement of the linear actuators, i.e. upon oscillation the oscillator plate 407 can slide within corresponding grooves provided within the holding portions 417. Still further, a holding member 419 is provided extending from the oscillator plate 407 such that this holding member can receive the immunoassay cartridge and support the same in a secured manner.

[0082] FIG. 2 further shows two buttons 601 and 603 for starting the action of the analyzer and two corresponding lights 605 and 607 indicating start and stop of the immunoassay. Thus, even untrained personnel can easily operate the analyzer 100 since it is only necessary to insert the immunoassay cartridge 200 into the analyzer 100 and press the shown buttons. The analyzer is then capable of performing the immunoassay, acquire the result images and analyze the same in a fully automated manner. Further, a control screen 609 is provided which may for example indicate a charging state of the batteries.

[0083] Inside printer housing 611, the analyzer is provided with a printer which preferably is a thermal printer. This printer can be used to print the results of the immunoassay. It was found that by the provision of this printer at the bottom of the analyzer, i.e. beneath the oscillator plate, the optical module 300 and the mechanical module 400 assures a compact and stable construction of the analyzer securing stability of the analyzer in particular during oscillations of the oscillator portion 407.

[0084] FIG. 3 shows an example of a lateral flow immunoassay strip 700. In the figure, a control line 703 is shown beside a test line 701 whereby the control line can be used to calibrate the acquired image. For example, the image of the strip taken with the CMOS or CCD sensor can be analyzed searching for the control line to determine the position of the result lines. Further, an absorbing pad 705 including for example antibodies is shown similarly as a pad 707 comprising sample and a pad 709 with remaining sample.

[0085] FIG. 4 illustrates examples of an immunoassay as may be visible through the result display section 213 of the immunoassay cartridge 200. The left portion of the figure illustrates a result which originally was in color. The right portion of the figure shows a treated result wherein the color result from the left portion of the figure was converted into grey scale. As can be taken from the figure, by the conversion into grey scale an increase of contrast can be achieved. For example, due to the increased contrast, on the right side of the figure, in result “1”, a line 800 “OPI” is clearly visible while to the left side, the same line in result “1” is less clear. Similarly, in result image “2”, a line 900 can be seen indicating “PCP” whereby the right portion of FIG. 4 clearly shows that by converting a color figure into a grey scale figure, the result contrast can be enhanced. Thus, in a preferred embodiment, the analyzer is adapted to perform image processing of images acquired by the two-dimensional sensor and the image processing includes a conversion of an image acquired from results displayed in the display section from a color image into a grey scale image.

[0086] FIGS. 5 and 6 illustrate results as shown in FIG. 4 converted into a corresponding curve whereby similar as in FIG. 4, the lines for OPI and PCP have been indicated by reference numerals 800 and 900.

[0087] FIG. 7 shows a flowchart illustrating a preferred method of image acquisition and processing and result interpretation. In a preferred embodiment, the analyzer is adapted to perform image processing of images acquired by the two-dimensional sensor and thereby adapted to perform steps, preferably all of the steps, as shown in FIG. 7. As shown, in step S101, an image is taken using the two-dimensional light sensor such as the CMOS sensor 301.

[0088] Upon image processing (step S200), bars are searched using a dedicated algorithm within the pixel matrix (step S201). From these bars, an angular deviation with respect to the horizontal orientation is determined (step S202).

[0089] Using for example the control line, the analysis area is selected (S203) wherein the result lines indicating the possible presence of drugs is selected. Further, the positions of the reading zones corresponding to the sections of the lateral flow strip are determined (S204).

[0090] Then, the results are converted from color scale into grey scale in order to increase the contrast (S205). In order to facilitate the processing, the information is compressed (S206) in order to obtain a data series with values between 0 and 255.

[0091] Upon analysis (S300), in order to assure comparability, the data sets are normalized (S301). In each of the data sets, minima are determined (S302) as they are illustrated in the above FIGS. 5 and 6. The corresponding minimum values are compared to predetermined threshold values such that the algorithm can automatically interpret the results (S303). Each data set is created in this manner (S304).

[0092] Upon interpretation of the results (S400), the validity of test is verified by varying if the control line is detected (S401).

[0093] Then, it is determined if lines are present in positions established for each drug (S402).

[0094] It is determined if the result is positive by determining the absence of a line (S403). In particular, using the above processing steps, advantageously an automatized acquisition and interpretation of the immunoassay results becomes possible.