METHOD OF DETECTING THE PRESENCE OF A BIOMARKER IN A SAMPLE OF A FLOWABLE SUBSTANCE AND A DETECTOR ASSEMBLY FOR USE IN THE DETECTION OF THE BIOMARKER IN THE SAMPLE

Abstract

In the detection of the presence of a biomarker or the like in a sample of a flowable substance, e.g. a powder or a liquid, usually a body fluid, such as blood, urine, or saliva, for example, a disposable sample receiver (3) is used, which has a receiving chamber (301) that is dimensioned to receive a predetermined volume and is surrounded by a depression (303) receiving any excess volume for which there is no room in the receiving chamber (301). The receiving chamber (301) has a bottom outlet (302) closed by a removable strip (33), e.g. a plastic strip or foil. Upon pulling away the strip (33) from the bottom outlet, the sample in the receiving chamber is emptied into a flow path (32) leading to at least one detection compartment (321) permitting direct visual inspection. Preferably, disposable sample receiver (3) is used in a detector assembly (1) including an electronic camera (23), a CPU (26) and a display (22). Hereby, the volume of the sample to be analyzed will always be the same, and by controlling the exact point of time when the sample is passed on into the flow path (32), a high degree of repeatability and accuracy is achieved, and thereby also a fail-safe system.

Claims

1. A method of detecting the presence of a biomarker in a sample of a flowable substance, said method comprising the steps of: providing a disposable sample receiver (3) having a receiving chamber (301), a bottom outlet (302) from the receiving chamber (301), a flow path (32) leading away from the bottom outlet (302); disposing the sample in the receiving chamber (301) and permitting the flowable substance to pass through the bottom outlet (302) into the flow path (32); providing a depression (303) surrounding the receiving chamber (301); filling the receiving chamber (301) until an excess of the flowable substance spills over into the depression (303); placing the disposable sample receive (3) in a place (25) of a detector assembly (1); and emptying the receiving chamber (301) by closing of a lid (21) of the detector assembly (1), thereby passing a protrusion (211) provided on the lid (21) through an opening (304) of the disposable sample receiver (3) to cause the flowable substance to flow from the receiving chamber (301) through the bottom outlet (302) and into the flow path (32)

2. A method as claimed in claim 1, wherein said flow path (32) comprises a permeable member (4), which prevents passage of at least one component of the flowable substance but permits passage of another one.

3. A method as claimed in claim 2, wherein said disposable sample receiver (3) comprises a directly visible detection compartment (321) located at the opposite end of said flow path (32) compared to the bottom outlet (302), wherein said detection compartment (321) is provided with a reagent which shifts color upon presence of a biomarker in the sample of flowable substance.

4. A method as claimed in claim 1, wherein said disposable sample receiver (3) comprises a directly visible detection compartment (321) located at the opposite end of said flow path (32) compared to the bottom outlet (302), wherein said detection compartment (321) is provided with a reagent which shifts color upon presence of a biomarker in the sample of flowable substance.

5. A method as claimed in claim 2, wherein the flowable substance is whole blood, and the permeable member (4) separates blood cells from plasma containing the biomarker.

6. A method as claimed in claim 3, wherein the flowable substance is whole blood, and the permeable member (4) separates blood cells from plasma containing the biomarker.

7. A method as claimed in claim 5, wherein the reagent is located in or downstream of the permeable member (4).

8. A method as claimed in claim 3, wherein the reagent is located in or downstream of the permeable member (4).

9. A method as claimed in claim 8, further comprising the steps of: analyzing the color shift by an electronic camera (23) and software (in 26), and showing the result on a display (22).

10. A detector assembly (1) for use in detection of the presence of a biomarker in a sample of a flowable substance, said assembly (1) comprising: a portable detector housing (2) having a place (25) for reception of a disposable sample receiver (3), and a disposable sample receiver (3) configured to be located in said place (25), said disposable sample receiver (3) comprising: (i) a receiving chamber (301) for reception of the sample of flowable substance, a bottom outlet (302) from the receiving chamber (301), a flow path (32) leading away from the bottom outlet (302); and (ii) a depression (303) surrounding the receiving chamber (301) that is dimensioned to receive a predetermined volume, said depression (303) receiving any excess volume for which there is no room in the receiving chamber (301); and wherein said detector housing (2) comprises a lid (21), provided with a protrusion (211) to activate the disposable sample receiver (3), whereby the sample of flowable substance enters the flow path (32).

11. A detector assembly (1) as claimed in claim 10, wherein said disposable sample receiver (3) comprises a directly visible detection compartment (321) located at the opposite end of said flow path (32) compared to the bottom outlet (302.

12. A detector assembly (1) as claimed in claim 11, wherein the detector housing (2) comprises equipment for analyzing color change marks of the biomarker to be detected, said equipment including an electronic camera (23), software (in 26), and a display (22) for displaying the result of the analysis.

13. A detector assembly (1) as claimed in claim 10, wherein the detector housing (2) comprises equipment for analyzing color change marks of the biomarker to be detected, said equipment including an electronic camera (23), software (in 26), and a display (22) for displaying the result of the analysis.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0051] In the following, the invention will be described in more detail with reference to preferred embodiments and the appended drawings.

[0052] FIG. 1 is an isometric view of a preferred embodiment of a detector assembly of the invention, including a detector housing and a disposable sample receiver.

[0053] FIG. 2 is an isometric view of the detector assembly of FIG. 2 from a slightly different angle and with a portion of the housing made transparent for showing its interior.

[0054] FIG. 3 is an isometric view of a top member of the disposable sample receiver of FIG. 1.

[0055] FIG. 4 is an isometric view of a bottom member of the disposable sample receiver of FIG. 1 and also shows an exploded view of a filter assembly that may be located in the bottom member.

[0056] FIG. 5 is a schematic longitudinal cross-sectional view of the disposable sample receiver of FIG. 1 showing inter alia a removable separating member in the shape of a strip having one end fixed to the receiver body and the other end sealing against a bottom outlet of a chamber for receiving the sample.

[0057] FIG. 6 is a view similar to FIG. 5 but showing how the removable separating member is removed from the bottom outlet to open the bottom outlet, so that the receiving chamber is emptied and part of the sample has arrived at the reactant for detection of the biomarker.

[0058] FIG. 7 is a longitudinal cross-sectional view of the top member of the disposable sample receiver of FIG. 1 showing a depression surrounding the receiving chamber.

[0059] FIG. 8 is a view of the underside of the bottom member of the disposable sample receiver of FIG. 1 showing a transparent window for inspection of a change of color in the reactant.

DETAILED DESCRIPTION OF VARIOUS EMBODIMENTS

[0060] The detector assembly 1 shown in FIG. 1 is a preferred embodiment of the present invention and is adapted for use in detection of the presence of a biomarker in a sample of a flowable substance, which usually is a body fluid, such as whole blood, urine, and saliva, for example. The assembly 1 includes a portable detector housing 2 having a place 25 for reception of a disposable sample receiver 3. It further includes a disposable sample receiver 3 adapted to be located in said place 25.

[0061] The disposable sample receiver 3 has a top member 30 shown in FIG. 3 and a bottom member 31 shown in FIG. 4. The top member 30 fits tightly on bottom member 31. FIG. 8 shows that the bottom member 31 on the outside of its wall has a plurality of locking projections 316, which are adapted to cooperate with a corresponding number of locking indentations 306 on the inside of the wall of the top member 30 shown in FIG. 7. Together, the projections 316 and the indentations 306 form snap locks. As is best shown in FIGS. 5-7, the top member 30 has a receiving chamber 301 for reception of the sample of flowable substance, and a bottom outlet 302 from the receiving chamber 301. When the top member 30 is fixed on the bottom member 31, a flow path 32 leading away from the bottom outlet 302 is defined between the top member 30 and the bottom member 31. A depression 303 surrounds the receiving chamber 301 that is dimensioned to receive a predetermined volume. The depression 303 is adapted to receive any excess volume for which there is no room in the receiving chamber 301. Thereby the analyzed amount of the sample is exactly the same each time an analysis is carried out.

[0062] As is best shown in FIGS. 5 and 6, the disposable sample receiver 3 further has a removable separating member 33 that is impermeable to the flowable substance and disposed at the bottom outlet 302 to keep the bottom outlet 302 sealed. Upon removal separating member 33 from the bottom outlet 302, the receiving chamber 321 is connected to the flow path 32, at the end of which a detection compartment 321 is located. In the embodiment shown in FIGS. 5 and 6, the detection compartment 321 is formed by a recess in the bottom member 31. If desired, the flow path 32 may split into a plurality of branches (not shown) and every branch has its own separate detection compartment 321.

[0063] In the preferred embodiment shown in FIGS. 5 and 6, the removable separating member 33 is an elongated strip, which according to one, non-limiting example is a substantially T-shaped plastic foil. One end 332 of the strip or foil 33 closes the bottom outlet 302 by forming a bottom of the receiving chamber 301, and the other end 331, i.e. the top portion of the “T”, is fixed to a body portion 305, 312 of the disposable sample receiver 3. In the preferred embodiment shown in FIGS. 4-6, the body portion 312 is formed by three posts extending upward from the bottom of the bottom member 31. The top of each post 312 has a reduced diameter, and the fixed end 333 of the removable strip or foil 33 has three matching holes for securing the fixed end 331 of the strip or foil 33 to the tops of the posts 312. To secure the strip or foil 33 to the posts 312, the top member 30 suitably is provided internally with three sockets 305 adapted to fit on the tops of the three posts 312.

[0064] Said elongated strip 33 may be of various materials, however according to one example it is made of 12 μm thick Hostaphan® WN from “Mitsubishi polyester film”, which is a translucent white film made of polyester, e.g. polyethylene terephthalate (PET) with high dielectric strength and large volume resistance and which can be easily formed in both warm and cold states.

[0065] Another conceivable example is 0.19 μm thick Mylar® A polyethyleneterephtalate-based transparent, flexible polyester film from Synflex, which is impervious to moist and solvents.

[0066] Both of the above examples of suitable materials for said elongated strip 33 provides impervious, yet flexible and pliable film materials which both prevents the flowable substance from exiting via the outlet 302, and also is flexible enough to be pulled away from the outlet. The skilled person understands that the above mentioned materials are merely two examples out of many, and that many other kinds of materials may be equally suitable for said elongated strip 33. The pulling away of the strip from the outlet will now be described in more detail.

[0067] FIGS. 4-6 also show that the bottom member 31 of the disposable sample receiver 3 further has an internal transversal support 311 for the strip 33. The internal support 311 is spaced from the fixed end 331 of the strip or foil 33 to form between them a space 313 under the strip or foil 33. The space 313 has a depth that is sufficient to permit the strip or foil 33 to be pressed into the space 313 a distance that will pull the sealing end 332 of the strip or foil 33 away from the bottom outlet 302 in order to empty the sample of flowable substance into the flow path 32 as illustrated in FIG. 6. As shown in FIG. 4, it is preferred that the internal support 311 is a transversal wall having at its top a recess 315 of a width and a depth that makes it suitable for guiding the strip or foil 33. Preferably, the strip or foil 33 is of a thickness that is sufficient to make it self-supporting but yet pliable enough to be pressed down into the space 313 to open the bottom outlet 302.

[0068] To press the strip or foil 33 into the space 313 as shown in FIG. 6, it is preferred that the top member 30 of the disposable sample receiver 3 has an opening 304 located above the space 313. Then, as shown in FIG. 1, it is also preferred that a device for pulling the sealing end 332 of the strip or foil 33 away from the bottom outlet 302 of the receiving chamber 301 includes a pivotal member 21 located on the detector housing 2 and provided with a protrusion 211 adapted to enter the opening 304 in order to press down the strip or foil 33 to remove it from the bottom outlet 302 and thereby let the flowable substance flow into the flow path 32.

[0069] In the preferred embodiment shown in FIG. 1, the pivotal member is a lid 21 that on shutting will cover the disposable sample receiver 3 and simultaneously pull away the strip 33 from the bottom outlet 302 to let the sample of flowable substance flow into the flow path 32, whereby every sample to be analyzed will be subjected to the same testing conditions with regard to volume and timing. Further, in the embodiment shown in FIG. 1 the detector assembly 1 has a separate pivotal locating lid 24 mounted under lid 21. As is best shown in FIG. 2, the locating lid 24 has an opening of a shape that matches the outer contour of the disposable sample receiver 3 to hold the sample receiver in an exact predetermined position on place 25, which in the shown embodiment is rectangular and larger than the disposable sample receiver 3.

[0070] At least upstream of the detection compartment 321, the flow path 32 preferably is provided with a permeable member 4, which prevents passage of at least one component of the flowable substance but permits passage of another one. In most cases said permeable member 4 suitably is a filter member that may include a plurality of individual filters. As pointed out above, although the flowable substance usually is a liquid, e.g. various body fluids, it could also be a powder. It is expected that in most cases the flowable substance will be blood, and that the permeable member 4, which usually is a filter, separates blood cells from plasma possibly containing a biomarker. If desired, the permeable member 4 may be a single filter member, for example. However, in the preferred embodiment of FIG. 4 it is a filter assembly 4 shown in an exploded view and comprising an uppermost receiving filter 40, at least one separation filter 41, and lowermost detection filter 42 that is adapted to be located in the detection compartment 321. As shown in FIG. 4, an end portion of the detection compartment 321 may be wider than the lowermost detection filter 42 to receive the component of the flowable substance that has passed through the entire filter assembly 4. The detection compartment 321 has a stop 322 to assist in the correct positioning of the lowermost detection filter 42. The filter assembly 4 has such a thickness that when it is placed in position in the disposable sample receiver 3, it will press the removable strip or foil 33 sealingly against the bottom outlet 302 of the receiving chamber 301, but yet permit the protrusion 211 of the pivotal lid 21 to pull the removable strip or foil 33 away from the bottom outlet to empty the receiving chamber 301 on the closing of the lid 21.

[0071] A reagent, which shifts color upon presence of the biomarker, may be provided in the flow path 32 and is then located in or downstream of the permeable member 4. When present, it is always located in the detection compartment 321, suitably in the lowermost detection filter 42 if such a one is provided.

[0072] To make a color shift in the detection compartment 321 directly visible, the bottom member 31 of the disposable sample receiver 3 may be transparent or just have a transparent portion 314 right under the detection compartment 321 as shown in FIG. 8. If desired, also the top member 30 may be made of transparent material. To assist the user of the detector assembly 1 in assessing any possible color shift in the detection compartment 321, it is preferred that the detector housing 2 as shown in FIG. 2 comprises an electronic camera 23 for taking a photo of the detection compartment 321 through the transparent portion 314 of the bottom member 31. The detector housing 2 further comprises a CPU 26, a display 22 and generally also at least one USB port 27. The photo is transmitted to the CPU 26, which after processing the data passes them on to the display 22. Preferably, a sensor (not shown) senses the closing of the lid 21 and sends a signal to the CPU 26 to start a timer when the lid protrusion 211 pulls away the removable strip or foil 33 from the bottom outlet 302 to empty the receiving chamber 301.

[0073] In this way, the exact point of time when the sample is passed on to the reagent (by removing the separating member 33 from the bottom outlet 302 of the receiving chamber 301) can be controlled, in combination with the depression 303 that is adapted to receive any excess volume for which there is no room in the receiving chamber 301 so that the analyzed amount of the sample is exactly the same each time an analysis is carried out, a high degree of repeatability and accuracy is achieved, and thereby also a fail-safe system.

[0074] 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 the teachings presented in the foregoing descriptions and the associated drawings. 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. Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation.

[0075] The present invention is applicable for use in detection of the presence of a biomarker or the like in a sample of a flowable substance, e.g. a powder or a liquid, usually a body fluid, such as blood, urine, or saliva, for example.