ARRANGEMENT FOR ANALYZING A LIQUID SAMPLE
20220280937 · 2022-09-08
Inventors
- Michael Schlaminger (Graz, AT)
- Wolf-Dietrich Steinböck (Graz, AT)
- Anton Hofer (St. Nikolai i. Sausal, AT)
Cpc classification
B01L2200/148
PERFORMING OPERATIONS; TRANSPORTING
B01L2300/0627
PERFORMING OPERATIONS; TRANSPORTING
B01L2400/0475
PERFORMING OPERATIONS; TRANSPORTING
B01L2300/0867
PERFORMING OPERATIONS; TRANSPORTING
B01L2200/026
PERFORMING OPERATIONS; TRANSPORTING
B01L3/502715
PERFORMING OPERATIONS; TRANSPORTING
International classification
Abstract
It is provided an arrangement and a method for measuring at least one constituent of a liquid sample, in particular comprising serum, plasma and/or urine, the arrangement comprising: a first portion adapted to partly delimit a reception space for the sample at a first side and comprising at least one measurement area; a second portion comprising: a reception space wall section, the second portion being coupled to the first portion such that the reception space wall section partly delimits the reception space at a second side; and a sample input cup delimiting a sample input region into which the sample is fillable, wherein the sample input region is in fluid communication with the reception space, wherein the reception space wall section and at least a portion of the sample input cup are integrally formed.
Claims
1. An arrangement for measuring at least one constituent of a liquid sample, the arrangement comprising: a first portion adapted to partly delimit a reception space for the sample at a first side and comprising at least one measurement area; a second portion comprising: a reception space wall section, the second portion being coupled to the first portion such that the reception space wall section partly delimits the reception space at a second side; and a sample input cup delimiting a sample input region into which the sample is fillable, wherein the sample input region is in fluid communication with the reception space, wherein the reception space wall section and at least a portion of the sample input cup are integrally formed.
2. The arrangement according to claim 1, wherein at least one of the following holds: the sample input cup comprises a sample input aperture at a top portion allowing insertion of one of a pipette and a capillary and a hollow needle; and the sample input cup is substantially rotationally symmetric with respect to a longitudinal axis of the sample input cup.
3. The arrangement according to claim 1, wherein at least one of the following holds: the sample input cup is bell shaped having an apex at a bottom portion; and an extent of a cross section of the sample input region perpendicular to the longitudinal axis decreases from the top portion to the bottom portion of the sample input cup, the sample input region being delimited by an inner face of the sample input cup; and the extent of a cross section of the sample input region close to or at the bottom portion of the cup is smaller than a diameter of a water drop having volume between 10 μl and 50 μl; and a diameter of the sample input region or sample input cup inner face increases by a factor of greater than two from bottom to top of the sample input cup.
4. The arrangement according to claim 1, wherein the sample input cup comprises at least one of at least one side inlet and at least one side outlet, having its longitudinal direction running in a direction including an angle between 30° and 60° with the longitudinal direction of the sample input cup.
5. The arrangement according to claim 4, the at least one of a side inlet and a side outlet allowing to provide at least one of a sample manifold and an inlet of working solution and an inlet of calibration solution and an inlet of washing solution and an outlet of waste solution or overflow liquid.
6. The arrangement according to claims 4, wherein at least one of the following holds: the at least one side inlet is oriented and positioned relative to the sample input cup such that liquid supplied by the side inlet discharges substantially tangentially to the inner face of the sample input cup into the sample input cup; and the longitudinal direction of the at least one side inlet is parallel to a tangential at the inner face of the sample input cup; and the side inlet is positioned such that liquid supplied by the side inlet into the sample input cup streams at a portion of the inner face of the sample input cup immediately adjacent to a liquid communication opening between the side inlet and sample input cup; and a liquid communication opening between the side inlet and sample input cup is above a liquid level of a reference amount of liquid filled into the sample input cup.
7. The arrangement according to claim 4, wherein the at least one side inlet comprises a first side inlet and a second side inlet arranged at different axial positions of the sample input cup, wherein the first side inlet and a second side inlet allow introduction of liquid into the sample input region in form of a spiral shaped stream at an inside surface of the sample input cup preventing cross-contamination.
8. The arrangement according to claim 7, wherein the side outlet includes an overflow outlet arranged axially above the first side inlet and second side inlet.
9. The arrangement according to claim 1, wherein the sample input cup comprises an output aperture at a bottom portion in a central region of the bottom portion, wherein the second portion comprises material below the output aperture configured to circumferentially delimit an input conduit providing fluid communication between the sample input region and the reception space, wherein an outer surface of material delimiting the input conduit serves as adherent surface at which the first portion is attached.
10. The arrangement according to claim 1, wherein the first portion and the second portion each comprise respective interface surface regions provided to form adherent surfaces at which the first portion and the second portion are mounted together.
11. The arrangement according to claim 10, wherein the interface surface region of the second portion is laterally offset from an input conduit axis of the input conduit towards the first side due to material delimiting the input conduit at the first side.
12. The arrangement according to claim 1, wherein the sample input cup comprises at least one of the following zones: a first zone at the bottom portion comprising a continuously changing diameter; a second zone at a middle portion comprising a substantially constant diameter and having one or more inlets; a third zone at a top portion comprising a continuously changing diameter or one or more step wise changes of the diameter.
13. The arrangement according to claim 12, wherein at least one of the following holds: an inner surface of the first zone includes an angle between 10° and 60° with a longitudinal axis of the sample input cup; and an inner surface of the second zone includes an angle between 0° and 10° with a longitudinal axis of the sample input cup; and an inner surface of the third zone includes an angle between 40° and 60° with a longitudinal axis of the sample input cup.
14. The arrangement according to claim 1, wherein the second portion is integrally formed manufactured by injection molding, using at least one of polycarbonate, polyester, polyamides and blends thereof.
15. The arrangement according to claim 1, wherein at least one of the following holds: the second portion further comprising, downstream the reception space, a reception space output port including a tube connector; and the measurement area comprises at least one analyte sensitive area, including an ion-selective electrode; and the arrangement including the sample input cup is configured to support direct ion selective electrode measurements of undiluted sample as input via the sample input cup.
16. The arrangement according to claim 15, further comprising at least one of: at least one suction pump, connected to the reception space output port; a liquid column separator connected to the suction pump, to receive liquid at an input port and configured to output the liquid via an output port, such that a continuous liquid column between the input port and the output port of the liquid column separator is interrupted.
17. The arrangement according to claim 16, the liquid column separator comprising: at least one guiding member having a guiding surface at which incoming liquid is collected and is guided to run downwards, at least one drip off edge at a bottom of the guiding member; a bottom collection region vertically spaced apart from and below the drip off edge, wherein the liquid column separator is formed by an upper member comprising the guiding member and formed by a lower member forming the bottom collection region.
18. The arrangement according to claim 17, wherein at least one of the following holds: for guiding the liquid two parallel and spaced apart guiding plates are provided between which the liquid is allowed to run downwards as a continuous liquid film; and an optical measurement is enabled in transmission through the transparent guiding plates and the liquid in between.
19. A method of measuring at least one constituent of a liquid sample, the method comprising: filling the sample into a sample input region delimited by a sample input cup; partly delimiting a reception space for the sample by a first portion at a first side, wherein the first portion comprises at least one measurement area; partly delimiting the reception space at a second side by a reception space wall section of a second portion coupled to the first portion; wherein the sample input region is in fluid communication with the reception space, wherein the reception space wall section and the sample input cup are integrally formed; the method further comprising: guiding the sample into the reception space; and measuring the sample in contact with the measurement area.
20. A method of manufacturing an arrangement for measuring at least one constituent of a liquid sample, the method comprising: manufacturing a first portion comprising at least one measurement area; manufacturing a second portion comprising a reception space wall section and a sample input cup; coupling the second portion to the first portion such that the reception space is delimited by the first portion at a first side, and such that the reception space is partly delimited by the reception space wall section at a second side; wherein the sample input cup is configured to delimit a sample input region into which the sample is fillable, wherein the sample input region is in fluid communication with the reception space, wherein the reception space wall section and at least a portion of the sample input cup are integrally formed.
Description
BRIEF DESCRIPTION OF THE DRAWING
[0064] Embodiments of the present invention are now described with reference to the accompanying drawings. The invention is not restricted to the illustrated or described embodiments.
[0065]
[0066]
[0067]
[0068]
DETAILED DESCRIPTION
[0069] The arrangement 1 for measuring at least one constituent of a liquid sample according to an embodiment of the present invention illustrated in
[0070] The arrangement 1, which may also be referred to as a measurement apparatus, further comprises a fluid transportation system 5 which is connected to a reception space output port 6 of the measurement cell 2. The fluid transportation system may be configured as a peristaltic pump. The fluid transportation system 5 is provided for aspiration and positioning of a liquid sample (for example patient sample) and/or working solution and/or calibrant solution, in fluid connection on a first end with the reception space output port 6 of the measurement cell 3 and on the second end in fluid communication with a liquid column separator 9 (also referred to as hose line separator) which will be described in detail below. Thus, the liquid column separator 9 is connected to the transportation system 5 or in particular the suction pump to receive liquid at an input port 10 and is configured to output the liquid via an output port 11 such that a continuous liquid column between the input port 10 and the output port 11 of the liquid column separator is interrupted. Thereby, the hose line separator or liquid column separator 9 electrically disconnects the measurement cell 3 from a closed column of conductive liquids and/or conductive coatings on the surface of tubings downstream from the liquid column separator 9, in particular the waste tubing 13, to avoid electrical interferences. The liquid column separator 9 is at the input port 10 in fluid communication with the fluid transportation system 5 and is connected at the output port 11 in fluid communication with the waste tubing 13. The waste tubing 13 connects the liquid column separator 9 and a waste compartment 14 which collects waste liquid.
[0071] The arrangement 1 further comprises a further fluid or liquid transportation system 15 provided for working solutions and calibrant solutions. The further transportation system 15 may typically comprise several peristaltic pumps in fluid connection (via tubing 16) with fluid compartments 17 holding working solutions and/or calibrants and on the other hand via tubing 18 to specific inlets 19 (in particular one or more inlets 19) leading to the interior 8 of the sample input cup 4. In the compartments 17, one or more containers for working solutions and/or calibrant solutions may be provided.
[0072] The arrangement 1 further comprises a control unit 20 which is communicatively connected to one or more of the other elements of the arrangement 1, in particular with the transportation systems 5 and/or 15 and with circuitry or electrodes of a measurement area 21 provided such that at least one sensitive area of the measurement area 21 is accessible from the reception space 7. The control unit 20 may be configured to acquire measurement data and may be configured to perform signal processing and/or system control and/or power supply and/or data exchange with an exterior equipment. In particular, the control unit 20 may be in electrical connection with the measurement cell 3, in particular the measurement area 21, and may be in electrical connection with one or more of the solution or liquid transport systems 5, 15.
[0073] The arrangement 1 is configured to support direct ISE methods and/or indirect ISE methods, in order to determine a plurality of ion activities of a liquid sample. The highly integrated measurement cell comprises a first portion (described below in detail) including all analyte electrodes and/or reference electrodes and/or sensors for fluidic control, in particular fluid and bubble detection and/or elements for thermostatic control and comprises a fluid channel including the reception space 7. The sample input cup 4 serves as sample compartment and/or sample manifold having specific inlets 19 for working solutions and/or calibrant.
[0074] The first portion 24 may be coupled to the second portion 22 by gluing at respective interface portions. The first portion 24 may be configured as a flat plate, in particular configured as a printed circuit board.
[0075] The sample input cup 4 delimits the sample input region 8 into which a sample or a calibration solution or a washing solution, for example may be filled. The second portion 22 comprises a reception space wall section (49, illustrated e.g. in
[0076]
[0077] The sample input cup 4 comprises a first side inlet 29 and a second side inlet 30 which are arranged at different vertical positions (and thus axial positions of the sample input cup 4). Further, these side inlets 29, 30 are arranged laterally at opposite sides of the sample input cup 4. The sample input cup 4 further comprises a side outlet 31 which is vertically above the first inlet 29 and the second inlet 30. As can be taken from
[0078]
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[0080] As can be appreciated from
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[0082] The inlets, in particular the first and second inlet 30, may be provided in a second zone 42 of the sample input cup 4, being vertically below the third zone 41. Within this zone 42, the diameter D may substantially be constant. The sample input cup 4 further comprises a first zone 43 at a bottom region which may also comprise the output aperture 35 leading to the input conduit 36. In the first zone, the diameter D may continuously change along the vertical direction. According to embodiments of the present invention, the sample input cup may comprise 1 or more of all these zones in any combination. For example, the sample input cup 4 does not necessarily comprise a zone having substantially constant diameter. The inlet 30 or further inlets may alternatively be connected or provided within the first zone and/or the third zone and the outlet.
[0083] Downstream the reception space 7 delimited by material of the second portion 22, a reception space output port 44 is provided having a tube connector 45 over which for example a flexible tubing may be drawn. The second portion 22 also partly delimits a region 46 branching off from the fluid connection path from the reception space 7 towards the reception space output port 44. Region 46 (an optional feature) forms a reservoir which acts as a compartment for the inner electrolyte of a reference electrode necessary for potentiometric measurement.
[0084] For loading, a liquid sample 47 (e.g. having filling level 60 below side inlets) contained within the sample input cup 4 into the reception space 7, the liquid is conveyed according to the flow direction 48 illustrated in
[0085]
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[0087] The guiding member 52 is formed by two parallel and spaced apart guiding plates 56, 57 as is illustrated in
[0088] According to embodiments of the present invention, the following features may apply to any of the aforementioned embodiments:
[0089] The fluid channel of the measurement cell may be provided with a rotationally symmetrically widening (as an example of a sample input cup) on a first end of the measuring channel which may serve as a sample compartment and/or sample manifold having specific inlets for a working solution and/or calibrant. The diameter of the inner face of the widening may increase at least one time from bottom to top.
[0090] The lower portion of the widening may be formed in a manner that aliquots of the test solution touch the inside of the rotationally symmetrically inner face, as a result of which drops that form on the tip of the sample transfer system, in particular a pipette, are fully captured by the inner face and a complete filling of the channel is guaranteed. This may enable to dispense very small volumes and to measure very small volumes of sample.
[0091] The upper portion of the widening may be formed in a manner that at least one supply line protrudes inclined tangentially into the rotationally symmetrically surface, whereas the distance between the supply line and the area with the minimum radius of the surface being selected so that no closed column of liquid is formed without active movement of the liquid. This may enable an electrical decoupling of the sensor area and the supply lines of the measurement cell which subsequently leads to increased interference immunity.
[0092] The inclined tangential coupling of the supply line may create a downswing spiral flow which may lead to a better cleaning of the inner face in contact with the test solution, in particular patient sample and calibrant and/or working solution. The sample input cup may comprise one or more supply lines. In case there are plural supply lines, the position of any of these supply lines or inlet ports may be selected so that both the distance between the lines and the resulting direction of the rotation of the spiral flow prevent cross contamination. The upper portion of the widening (for example supply sample input cup) may be formed in a manner to prevent overflow and/or mitigate the effects of an overflow and/or leakage of test solution, in particular patient sample and/or calibrant and/or working solution. This may be achieved by an additional increase of the diameter of the inner face of the widening and/or by having a drain line protruding the inner face, through which the liquid can be drained off in a targeted manner.
[0093] The second end of the flow channel may be in fluid communication with a fluid transportation system which may be in immediate vicinity of the second end of the channel.
[0094] The measurement cell, in particular the flow channel, may be integrally formed, in particular manufactured by injection moulding, further in particular using polycarbonate, polyester, polyamides and blends thereof. This may enable the integration of a sample compartment and/or sample manifold having specific inlets for working solution and/or calibrant into a consumable which can be replaced at a regular base without having economical drawbacks. Further, this may enable that long-term effects such as overlay coating and/or surface modification coating of biological samples, in particular biofouling, can be avoided by cyclical replacement and does not require extensive cleaning and/or other maintenance activities at a regular base, yielding into higher uptime of the system and minimized user interaction.
[0095] The fluid transportation system (for example illustrated in
[0096] The liquid column separator 5 or also called hose line separator 5 may be composed of at least two hollow bodies which may be connected in such a way that the liquid drips of, thereby interrupting a closed column of liquid, whereas the diameter of the inner face of the lower body exceeds the inner face of the upper body and the delimitation of the inner surface of the upper body penetrates the inner volume of the lower body. Thereby, an edge (for example edge 53 illustrated in
[0097] The body of the liquid column separator may be shaped in such a way that two plane parallel transparent surfaces (for example 56, 57 illustrated in
[0098] The measurement cell may for example be replaced on a regular base or after a predefined number of measurements have been performed.
[0099] It should be noted that the term “comprising” does not exclude other elements or steps and the use of articles “a” or “an” does not exclude a plurality. Also elements described in association with different embodiments may be combined. It should also be noted that reference signs in the claims should not be construed as limiting the scope of the claims. Further, spatially relative terms, such as “front” and “back”, “above” and “below”, “left” and “right”, et cetera are used to describe an element's relationship to another element(s) as illustrated in the Figures. Thus, the spatially relative terms may apply to orientations in use which differ from the orientation depicted in the Figures. Obviously all such spatially relative terms refer to the orientation shown in the Figures only for ease of description and are not necessarily limiting as an apparatus according to an embodiment of the invention can assume orientations different than those illustrated in the Figures when in use.