(19)
(11)EP 3 145 634 B1

(12)EUROPEAN PATENT SPECIFICATION

(45)Mention of the grant of the patent:
19.08.2020 Bulletin 2020/34

(21)Application number: 15721722.5

(22)Date of filing:  12.05.2015
(51)Int. Cl.: 
B01L 3/00  (2006.01)
G01N 21/03  (2006.01)
A61B 5/15  (2006.01)
(86)International application number:
PCT/EP2015/060505
(87)International publication number:
WO 2015/177004 (26.11.2015 Gazette  2015/47)

(54)

SAMPLING AND ASSAY KIT, SAMPLE HOLDER AND METHOD

ABTASTUNGS- UND TESTSATZ, PROBENHALTER UND VERFAHREN

KIT D'ÉCHANTILLONNAGE ET DE DOSAGE, PORTE-ÉCHANTILLON ET PROCÉDÉ


(84)Designated Contracting States:
AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

(30)Priority: 21.05.2014 EP 14169315

(43)Date of publication of application:
29.03.2017 Bulletin 2017/13

(73)Proprietor: Aidian Oy
02200 Espoo (FI)

(72)Inventors:
  • LAUKKONEN, Jukka
    02101 Espoo (FI)
  • RAUSSI, Jaana
    02101 Espoo (FI)
  • EILOLA, Sanna
    FI-01710 Vantaa (FI)
  • RISSANEN, Jaakko
    FI-02180 Espoo (FI)

(74)Representative: J A Kemp LLP 
14 South Square Gray's Inn
London WC1R 5JJ
London WC1R 5JJ (GB)


(56)References cited: : 
EP-A1- 0 638 803
EP-B1- 0 859 664
EP-B1- 1 628 770
WO-A1-2014/072170
US-A1- 2010 255 460
US-A1- 2012 214 251
EP-B1- 0 859 664
EP-B1- 1 628 770
WO-A1-2014/072170
US-A- 5 833 630
US-A1- 2012 214 251
US-A1- 2013 065 245
  
      
    Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted. Notice of opposition shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention).


    Description


    [0001] This invention relates to sampling and assay kits, and use of sample holders in such kits. The invention has particular, although not exclusive, relevance to sample holders and sampling and assay kits, for use in clinical tests on biological fluids, such as blood.

    [0002] In such tests, the biological fluid is collected and typically mixed with a reagent and a buffer. The reagent might be in liquid or solid form. A quantitative assay of the biological sample and reagent within the buffer typically utilises an analyser equipment using optical measurement techniques, in which a light beam or laser beam is directed through the mixture and a signal indicative of the optical properties of the sample, such as absorbance, reflectance, fluorescence, phosphorescence, luminescence and so on, is obtained.

    [0003] In such quantitative assay techniques, it is necessary for the biological sample which has been freshly obtained, usually by a clinician, to be mixed with the reagent and the buffer in very accurate proportions. In order to provide such accurate proportions, it is known to provide sampling and assay kits which already include premeasured amounts of the reagent and the buffer.

    [0004] One such test kit is disclosed in European patent specification EP 0859664. This document discloses a sampling and assay kit. In such an assay kit the biological sample is obtained by a capillary, which is discharged to a buffer present in a measuring cuvette by a plunger of the capillary. The measuring cuvette is closed with a cuvette closure device including a body part which has a sealed reagent storage chamber in a space between the lid of the body part and the plunger. A pre-measured amount of a reagent is stored in a reagent storage chamber of the closure device. Pressure by an operator, depresses the plunger of the device, so as to force a lower lid of the closure device to open, enabling discharge of the reagent into the buffer present in the cuvette.

    [0005] An alternative arrangement is disclosed in WO 2005/071388, which discloses a sampling and assay device comprising at least three chamber portions, connected together in a row. One end chamber is capable of receiving a biological sample. The middle chamber contains reagent for forming the assay. A final portion of the device comprises a reaction chamber, including a buffer. The reaction chamber is inserted into an assay device, to enable an optical analysis of the enclosed buffer, reagent and biological sample to be performed.

    [0006] WO 2009/118444 discloses an assay device, comprising a container including a sealed chamber, bounded on at least one side by a penetrable member. A sampler having a capillary passage for receiving the biological sample is provided, the sampler having a means configured to penetrate the penetrable member, to enable passage of the biological sample into the sealed chamber.

    [0007] US 5 833 630 discloses a sample collection device comprising a capillary holder for holding a blood sample, the capillary holder being insertable within a cuvette containing a reagent liquid. A pressure cap may be used to cause the capillary holder to be pushed into the cuvette.

    [0008] US 2012/214251 discloses a test set for a photometric measuring device, where sample-taking device is integrated on a dosing container which may be inserted in a sealing manner into a filling opening of a mixing container.

    [0009] US 2013/0302219 discloses devices for collection and elution of oral fluid samples by using a handle having a collection pad which is inserted into a collection tube. There is an adaptor in the collection tube with a narrowed portion for wringing a sample from the pad.

    [0010] US 3 475 127 discloses a sample measuring device for measuring precise volumes of fluid samples. A blood sample is collected within a capillary tube, the tube being provided with scored notches or grooves. The capillary tube is broken along a score line and the blood filled segment of the capillary tube is placed in a vessel including a reagent for analysis.

    [0011] US 2008/0193926 discloses a device for extracting a smear sample. The smear sample is carried to a cavity with a sample carrier. A cotton swab may be used to introduce the sample to the cavity and then the cotton swab may be broken.

    [0012] WO 2014/077170 discloses a test set for a photometric measuring device, comprising a mixing container which has a filling opening and comprising a metering container which can be sealingly inserted into the filling opening of the mixing container and which contains a liquid reagent in a closed cavity. The cavity has a closure plunger, which can be moved axially in the cavity, at a first end of the metering container, said closure plunger generating a specifiable filling pressure in the reagent, and the metering container has a closure membrane at a second metering container end which can be inserted into the mixing container. According to the invention, the closure membrane is equipped with a predetermined breaking point which breaks open when the filling pressure is exceeded in a defined manner as a result of an axial movement of the closure plunger, said predetermined breaking point of the closure membrane being formed as a linearly extending material taper of the closure membrane, wherein the taper is arranged eccentrically in the region of an opening in the base of the substantially cylindrical metering container.

    [0013] Such known sampling and assay kits, have the disadvantage that sample collection, transfer and mix with a reagent buffer might be difficult for a time pressured clinician. It is an object of the present invention, to provide a sampling and assay kit, and the use of a sample holder in such a kit which address easier and quicker sample collection, transfer and mix with a reagent buffer.

    [0014] According to a first aspect of the present invention there is provided a sampling and assay kit according to claim 1.

    [0015] By such an arrangement, predetermined quantities of the components forming the sample to be analysed may be provided.

    [0016] According to a second aspect of the present invention there is provided a use of a sample holder in a sampling and assay kit, in accordance with claim 7.

    [0017] A sampling and assay kit, a method and a sample holder, will now be described by way of example only, with reference to the accompanying drawings in which:

    Figure 1 is a schematic cross-section of a sample holder in accordance with a first embodiment of the invention, for use in a sampling and assay kit in accordance with the first embodiment;

    Figure 2 is a schematic cross-section of a cuvette holding the sample holder shown in Figure 1, showing the insertion of a stopper;

    Figure 3 is a schematic overview of the sampling and assay test kit of Figures 1 and 2, inserted in a test apparatus; and

    Figure 4 is a schematic cross-section of a sample holder in accordance with the second embodiment of the invention for use in a sampling and assay kit in accordance with the second embodiment;

    Figure 5 shows the sample holder of Figure 4, in which part of the handle has been separated from the rest of the sample holder;

    Figure 6 is a schematic cross-section of a cuvette holding the sample holder shown in Figure 5, showing the insertion of the stopper; and

    Figures 7(a)-7(e) are schematic presentations of the steps of a method of collecting and transferring a sample, in accordance with the second embodiment of the invention, using the sampling and assay kit shown in Figures 4 to 6.



    [0018] Referring firstly to Figures 1 and 2 the first embodiment of an assay kit in accordance with the invention comprises three separate portions:

    a sample holder 1 including a capillary tube 4;

    a cuvette 6; and

    a stopper 7.



    [0019] Referring now also to Figure 3, in use of the sampling and assay kit, the sample holder 1 is placed in the cuvette 6, so that a sample within the capillary tube 4 is able to dilute to a liquid in the cuvette 6. Measurement of the sample is based on a photometric, preferably turbidometric method, as described in more detail later. Thus the cuvette 6 is inserted in a test apparatus 9 arranged to direct a beam of light, or radiation through the analyte present in the measuring zone 11 in the cuvette 6. The amount of light or radiation passing through the analyte is measured by a detector 12 and used to provide an analysis of the analyte.

    [0020] The three portions of the assay kit will now be described in more detail.

    [0021] Referring firstly particularly to Figure 1, the sample holder 1 has a tubular body portion 3 in which the upper open end of capillary tube 4 is mounted. The top of the tubular body 3 is formed with two projections in the form of shoulders 10A, 10B whose function will be described hereafter, an indented area 13 being defined between the shoulders 10A, 10B. It will be appreciated that the capillary may be molded with the body part as a single part, as an alternative to being mounted in the body part.

    [0022] Referring now particularly to Figure 2, the lower part of this figure shows the sample holder 1 after it has been inserted in the cuvette 6. The cuvette 6 may be prefilled with a liquid 14 for diluting the sample from the capillary 4. This may be a buffer solution, for example and preferably will produce a clear solution in the cuvette 6 when mixed with the sample. The buffer solution may be any suitable buffer solution. Preferably, the buffer solution might be tris buffer or phosphate buffer. The buffer may contain some reagents, for example haemolysing compound.

    [0023] The cuvette 6 has an inwardly facing ledge 15 on which, in use, the shoulder portions 10A, 10B of the body portion 3 of the sample holder 1 rest, so as to maintain the sample holder 1 accurately in position in the cuvette 6, with the end of the capillary tube 4 being positioned in the liquid 14 within the cuvette 6 to enable the sample to pass from the capillary 4 into the liquid 14, but with the capillary tube 4 being positioned above the measuring zone 11.

    [0024] Referring now particularly to Figure 2, and described in more detail in our previous application EP 0859664, the stopper 7 includes a chamber 16 in which a premeasured amount of a reagent may be stored, a lower lid 17, an externally threaded portion 18 and a plunger 19. The reagent may be of any suitable form, either liquid or solid. Examples of reagents are an analyte binding reagent (e.g. antibodies), solid particles, haemolysing compound (saponin) or red blood cells agglutinating compound (lectin).

    [0025] Depression of the plunger 19 causes a downward movement of the lower lid 17, enabling ejection of the reagent stored in the chamber 16. Figure 2 illustrates the lower lid 17 in an opened state outside the cuvette 6. When the stopper 7 is inserted into the cuvette 6, the externally threaded portion 18 of the stopper 7 acts as a seal and maintains the stopper 7 in place at the top of the cuvette 6.

    [0026] The indented portion 13 of the sample holder 1 gives sufficient space within the cuvette 6 for the lower lid 17 of the stopper 7 to be opened within the cuvette 6 when the sample holder 1 is positioned within the cuvette 6. This enables the reagent stored in the compartment 16 to pass to the liquid 14 in the base of the cuvette 6.

    [0027] As in use of the assay kit, the capillary tube 4 is held in place above the base of the cuvette 6, by the projections 10A, 10B of the sample holder resting on the inward facing ledge 15 of the cuvette 6, the capillary tube 4 is kept out of the light or radiation path through the cuvette 6. Thus, although the blood sample is able to pass into the buffer solution from the capillary tube 4, the presence of the capillary tube does not affect the optical measurement of the analyte in the measuring zone 11.

    [0028] It will be appreciated that whilst in the embodiment described, the sample holder 1 has two projections in the form of shoulders 10A, 10B which rest on the inwardly formed ledge 15 in the cuvette 6, the sample holder 1 may have a different number of projections, or may be formed with a continuous projection which may rest on the ledge 15 in the cuvette 6.

    [0029] Referring now to Figures 4 to 7, the second embodiment of an assay kit in accordance with the invention is an adaptation of the assay kit described in the first embodiment and thus corresponding features are correspondingly labelled.

    [0030] However as shown in Figure 4 the sample holder 21 in the second embodiment has a removable handle portion 22 which is attached, via a cylindrical spur 24, to the tubular body portion 3 in which the upper open end of capillary tube 4 is mounted. As in the first embodiment, the top of the tubular body 3 is formed with two projections in the form of shoulders 10A, 10B, with an indented area 13 being defined between the shoulders 10A, 10B.

    [0031] The removable handle portion 22 is detachable from the rest of the sample holder 21 as indicated in Figure 5. The detachment may be achieved by twisting the removable handle portion 22 at the cylindrical spur 24 to separate handle portion 22 from the body portion 3, so as to leave behind a stub on the intended area 13 on the body portion 3 as shown in Figure 5.

    [0032] Referring now particularly to Figure 6, the lower part of this figure shows the sample holder 21 after it has been inserted in the cuvette 6, with the removable handle portion 22 of the sample holder 21 removed as described above.

    [0033] As in the first embodiment, the cuvette 6 has an inwardly facing ledge 15 on which, in use, the shoulder portions 10A, 10B of the body portion 3 of the sample holder 21 rest, so as to maintain the sample holder 21 accurately in position in the cuvette 6, with the end of the capillary tube 4 being positioned in the liquid 14 within the cuvette 6 to enable the sample to pass from the capillary 4 into the liquid 14, but with the capillary tube 4 being positioned above the measuring zone 11.

    [0034] As in the first embodiment, depression of the plunger 19 causes a downward movement of the lower lid 17, enabling ejection of the reagent stored in the chamber 16. Figure 6 illustrates the lower lid 17 in an opened state outside the cuvette 6, removal of the removable handle portion 22 from the rest of the sample holder 21 allowing the stopper 7 to be inserted in the cuvette 6 in the space above the tubular body part 3 of the sample holder 21 as shown in Figure 6. As in the first embodiment, the stopper 7 is inserted into the cuvette 6, the externally threaded portion 18 of the stopper 7 acting as a seal and maintaining the stopper 7 in place at the top of the cuvette 6.

    [0035] Referring now to Figure 7, this figure illustrates the use by a clinical operator, of the sample and assay kit in accordance with the second embodiment of the invention.

    [0036] Referring firstly to Figure 7(a), the clinical operative will remove a foil seal from the cuvette.

    [0037] Referring now to Figure 7(b), a blood sample is collected from a finger of a patient to the capillary 4 of the sample holder 21, by using the handle portion 22 to manipulate the capillary tube 4, without contaminating the sample. The blood sample will be drawn up the capillary tube 4 by capillary action.

    [0038] Referring now to Figure 7(c), the handle portion 22 may be used to transfer the sample holder 21 into the cuvette 6, the sample holder 21 hanging within the cuvette 6 by the projections in the form of shoulder portions 10A, 10B of the sample holder 1 resting on the inward ledge 15 of the cuvette as described above. This allows the blood sample to pass from the capillary tube 4 into the liquid 14 present in the cuvette 6. By twisting the handle portion 22, the handle portion 22 of the sample holder 21 may be removed from the body portion 3 of the sample holder 21, as described above.

    [0039] Referring now to Figure 7(d) the stopper is placed in the cuvette 6, with the lower lid 17 of the stopper 7 in a closed state, so that the reagent enclosed within the chamber 16 in the stopper is maintained within the chamber 16.

    [0040] Finally, referring to Figure 7(e), the cuvette 6 including the sample holder 21 with the handle portion 22 removed and the stopper 7, is then placed into the test apparatus 9. The plunger 19 in the stopper 7 is pressed and the lower lid 17 of the stopper 7 is opened, allowing the reagent held in the chamber 16, to be released from the chamber 16, to pass the sample holder 21 and subsequently to pass into the base of the cuvette 6.

    [0041] Thus the mixture in the base of the cuvette 6, that is in the measuring zone 11, may be measured optically as described above in relation to Figure 3 and the presence, or concentration, of an analyte in the liquid at the base of the cuvette 6 determined, using for example spectrophotometry.

    [0042] It will be appreciated that whilst the removable handle portion 22 and the tubular body portion 3 are connected by a cylindrical spur 5 in the second embodiment, other weakened portions between the handle portion 22 and tubular body portion 3 of the sample holder 21 may be provided to enable removal of the handle portion 22. Examples of such alternative arrangements include a perforated section of the sample holder 21.

    [0043] It will be appreciated that the form of the handle portion 22 particularly enables easier handling of the sample holder 21 for sample collection. However, the sampling and assay kit may be used in other applications. Transfer of samples other than blood samples, for example from sample vials, or liquid transfer from for example reagent bottles comprising standard or reference solutions is also made easier.

    [0044] Whilst the sample collecting device described in the above embodiments is a capillary tube 4, other sample collection arrangements are possible in a sample and assay kit in accordance with the invention, for example a swab. The capillary tube 4 maybe itself coated with a reagent, for example heparin.

    [0045] It will be appreciated that the sample holder 1 or 21 and cuvette 6 may be provided as a kit. The kit may further include the stopper 7. Whilst it is advantageous to provide preloaded quantities of the buffer and reagent in the cuvette 6 and stopper 7, these may be provided separately.


    Claims

    1. A sampling and assay kit comprising a separate stopper (7), receptacle (6) and sample holder (1; 21):

    the receptacle (6) being for holding a quantity of a liquid;

    the sample holder (1; 21) comprising:

    a sampler (4); and

    a body portion (3), which holds the sampler (4) and is insertable within the receptacle (6), the body portion (3) including projection means in the form of shoulders (10A, 10B);

    wherein the receptacle (6) has an internal projection (15) such that when the body portion (3) is inserted in the receptacle (6), the projection means (10A, 10B) of the body portion (3) rests on said internal projection (15), so as to cause positioning of the sampler (4) within the receptacle (6) at a predetermined position above the end of the receptacle (6);

    the stopper (7) including a chamber (16) for holding a reagent, a lid (17) and a plunger device (19) effective to open the lid (17), said body portion including an indented portion (13) being defined between the shoulders (10A, 10B), which enables opening of the lid (17) so as to enable ejection of reagent held within the chamber (16) into the receptacle (6) when the stopper (7) is inserted in the receptacle (6) in a space above the body portion.


     
    2. A sampling and assay kit according to claim 1 wherein said predetermined position is such that, in use, part of the sampler (4) is within said liquid, but above a measuring zone (11) for performing an optical analysis of the contents of the receptacle (6).
     
    3. A sampling and assay kit according to claims 1 or 2 wherein said sampler is a capillary tube (4).
     
    4. A sampling and assay kit according to any one of the preceding claims wherein said receptacle comprises a cuvette (6).
     
    5. A sampling and assay kit according to any one of the preceding claims wherein said liquid is a buffer solution.
     
    6. A sampling and assay kit according to any one of the preceding claims wherein said sample is a blood sample.
     
    7. The use of a sample holder in a sampling and assay kit according to claim 1.
     


    Ansprüche

    1. Probenahme- und Testkit, umfassend einen separaten Stopfen (7), einen Behälter (6) und einen Probenträger (1; 21):

    wobei der Behälter (6) dazu dient, eine Menge einer Flüssigkeit aufzunehmen;

    wobei der Probenträger (1; 21) Folgendes umfasst:

    einen Probenehmer (4); und

    einen Körperabschnitt (3), der den Probenehmer (4) aufnimmt und in den Behälter (6) einsetzbar ist, wobei der Körperabschnitt (3) Vorsprungmittel in Form von Schultern (10A, 10B) umfasst;

    wobei der Behälter (6) einen inneren Vorsprung (15) aufweist, sodass das Vorsprungmittel (10A, 10B) des Körperabschnitts (3), wenn der Körperabschnitt (3) in den Behälter (6) eingesetzt wird, auf dem inneren Vorsprung (15) bleibt, sodass ein Positionieren des Probenehmers (4) in dem Behälter (6) an einer vorbestimmten Position oberhalb des Endes des Behälters (6) verursacht wird;

    der Stopfen (7) eine Kammer (16) zum Aufnehmen eines Reagens, einen Deckel (17) und eine Kolbenvorrichtung (19), die wirksam ist, um den Deckel (17) zu öffnen, umfasst, wobei der Körperabschnitt einen vorgesehenen Bereich (13), der zwischen den Schultern (10A, 10B) definiert ist, umfasst, der ein Öffnen des Deckels (17) ermöglicht, um einen Ausstoß von Reagens, das in der Kammer (16) aufgenommen ist, in den Behälter (6) zu ermöglichen, wenn der Stopfen (7) in einem Bereich oberhalb des Körperabschnitts in den Behälter (6) eingesetzt wird.


     
    2. Probenahme- und Testkit nach Anspruch 1, wobei die vorbestimmte Position so ist, dass ein Teil des Probenehmers (4) sich bei Verwendung in der Flüssigkeit, jedoch oberhalb einer Messzone (11) zum Durchführen einer optischen Analyse des Inhalts des Behälters (6) befindet.
     
    3. Probenahme- und Testkit nach den Ansprüchen 1 oder 2, wobei der Probenehmer ein Kapillarrohr (4) ist.
     
    4. Probenahme- und Testkit nach einem der vorstehenden Ansprüche, wobei der Behälter eine Küvette (6) umfasst.
     
    5. Probenahme- und Testkit nach einem der vorstehenden Ansprüche, wobei die Flüssigkeit eine Pufferlösung ist.
     
    6. Probenahme- und Testkit nach einem der vorstehenden Ansprüche, wobei die Probe eine Blutprobe ist.
     
    7. Verwendung eines Probenträgers in einem Probenahme- und Testkit nach Anspruch 1.
     


    Revendications

    1. Kit d'échantillonnage et d'analyse, comprenant un bouchon séparé (7), un réceptacle (6) et un porte-échantillon (1 ; 21) :

    le réceptacle (6) étant pour contenir une quantité d'un liquide ;

    le porte-échantillon (1 ; 21) comprenant :

    un échantillonneur (4) ; et

    une portion corps (3), qui retient l'échantillonneur (4) et est insérable à l'intérieur du réceptacle (6), la portion corps (3) incluant des moyens de saillie sous la forme d'épaulements (10A, 10B) ;

    dans lequel le réceptacle (6) a une saillie interne (15) de telle sorte que, lorsque la portion corps (3) est insérée dans le réceptacle (6), les moyens de saillie (10A, 10B) de la portion corps (3) reposent sur ladite saillie interne (15), afin de causer le positionnement de l'échantillonneur (4) à l'intérieur du réceptacle (6) à une position prédéterminée au-dessus de l'extrémité du réceptacle (6) ;

    le bouchon (7) incluant une chambre (16) pour contenir un réactif, un couvercle (17) et un dispositif piston plongeur (19) efficace pour ouvrir le couvercle (17), ladite portion corps incluant une portion en retrait (13) définie entre les épaulements (10A, 10B), qui permet l'ouverture du couvercle (17) afin de permettre l'éjection de réactif, contenu à l'intérieur de la chambre (16), dans le réceptacle (6) lorsque le bouchon (7) est inséré dans le réceptacle (6) dans un espace au-dessus de la portion corps.


     
    2. Kit d'échantillonnage et d'analyse selon la revendication 1, dans lequel ladite position prédéterminée est telle que, durant l'utilisation, une partie de l'échantillonneur (4) soit à l'intérieur dudit liquide, mais au-dessus d'une zone de mesure (11) pour réaliser une analyse optique des contenus du réceptacle (6).
     
    3. Kit d'échantillonnage et d'analyse selon les revendications 1 ou 2, dans lequel ledit échantillonneur est un tube capillaire (4).
     
    4. Kit d'échantillonnage et d'analyse selon l'une quelconque des revendications précédentes, dans lequel ledit réceptacle comprend une cuve cylindrique (6).
     
    5. Kit d'échantillonnage et d'analyse selon l'une quelconque des revendications précédentes, dans lequel ledit liquide est une solution tampon.
     
    6. Kit d'échantillonnage et d'analyse selon l'une quelconque des revendications précédentes, dans lequel ledit échantillon est un échantillon sanguin.
     
    7. Utilisation d'un porte-échantillon dans un kit d'échantillonnage et d'analyse selon la revendication 1.
     




    Drawing


















    REFERENCES CITED IN THE DESCRIPTION



    This list of references cited by the applicant is for the reader's convenience only. It does not form part of the European patent document. Even though great care has been taken in compiling the references, errors or omissions cannot be excluded and the EPO disclaims all liability in this regard.

    Patent documents cited in the description