CA1252701A - Cuvette - Google Patents

Cuvette

Info

Publication number
CA1252701A
CA1252701A CA000465095A CA465095A CA1252701A CA 1252701 A CA1252701 A CA 1252701A CA 000465095 A CA000465095 A CA 000465095A CA 465095 A CA465095 A CA 465095A CA 1252701 A CA1252701 A CA 1252701A
Authority
CA
Canada
Prior art keywords
cuvette
semipermeable membrane
cavity
reagent
membrane
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
CA000465095A
Other languages
French (fr)
Inventor
Jan E. Lilja
Sven E.L. Nilsson
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
ANTIEBOLAGET LEO
Original Assignee
ANTIEBOLAGET LEO
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=20352930&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CA1252701(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by ANTIEBOLAGET LEO filed Critical ANTIEBOLAGET LEO
Application granted granted Critical
Publication of CA1252701A publication Critical patent/CA1252701A/en
Expired legal-status Critical Current

Links

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/04Closures and closing means
    • B01L2300/046Function or devices integrated in the closure
    • B01L2300/048Function or devices integrated in the closure enabling gas exchange, e.g. vents
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • B01L2300/0627Sensor or part of a sensor is integrated
    • B01L2300/0645Electrodes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • B01L2300/0681Filter
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0822Slides
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0864Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0403Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406Moving fluids with specific forces or mechanical means specific forces capillary forces
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03Cuvette constructions
    • G01N2021/0346Capillary cells; Microcells
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N2021/775Indicator and selective membrane
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03Cuvette constructions
    • G01N21/0332Cuvette constructions with temperature control
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00Chemistry: molecular biology and microbiology
    • Y10S435/81Packaged device or kit

Abstract

CANADIAN PATENT APPLICATION

OF

JAN EVERT LILJA and SVEN ERIK LENNART NILSSON

FOR

CUVETTE

Abstract of the Disclosure:

This invention relates to a new disposable cuvette for essentially simultaneous sampling of a fluid and analysing the sample. The new cuvette comprises a body member having at least one cavity defined by surrounding walls, into which cavity the sample is permitted to enter by capillary force through an inlet communicating said cavity with the exterior of the body member. According to the invention, the cuvette is characterised in that at least a portion of the walls facing the cavity consists of a semipermeable membrane, optionally with an ihtegrated electrode and/or sensor system, and that at least one reagent or reagent system is incorporated in the cuvette.

Description

l ~Z'7~1 The present invention concerns a disposabie cuvette for essentially simultaneous sampling of a fluid and analysing the sample.
A cuvette for sampling a fluid, mixing the sample with a reagent and directly making optical analyses of the sample mixed with the reagent is previously known from US Patent 4,088,448. This cuvette comprises a body member including two planar surfaces defining an optical path and placed at a predetermined distance from one another to determine the optical path length and to define a cavity having an inlet communicating said cavity with the exterior of the body member.
The cavity has a predetermined fixed volume, and the predetermined distance permits the sample to enter the cavity by capillary force. Furthermore, a reagent is coated on the cavity surface.
This known cuvette has several advantages when compared with the conventionally used devices. It permits sampling of a liquid, mixing and chemically reacting it with a suitable reagent for e.g. colour development in the same vessel as the one used for the subsequent measurement. The cuvette disclosed in US Patent 4,088,448 thus simplifies the sampling procedure, reduces the number of utensils and - in most cases, depending on the type of anaylysis - con-siderably improves the accuracy of analysis by making the analysing procedure independent of the operating technique of the operator making the analysis.
2 ~$

lZSZ7~
The present invention concerns an improvement of this known cuvette.
To this end, there has been developed a disposable cuvette for simultaneously sampling a fluid and analysing the sampled fluid. The cuvette includes a body member having an exterior and at least one cavity defined by surrounding walls. An inlet in the walls communicates with the cavity through the exterior of the body member and through which the sampled fluid can enter the cavity by capillary forces. At least one of the walls includes a semipermeable membrane having one surface defining a portion of the cavity and an opposite surface forming an external surface of the cuvette.
The semipermeable membrane has a predetermined porosity and thereby functions as a discriminator to permit entry only of molecules/ions up to certain size. At least one reagent is incorporated in the cuvette in contact with the semipermeable membrane.

One advantage of the improved cuvette is that it can be used for other types of measurements than optical analyses, which makes it applicable to analyses within a much broader range than the cuvette according to US Patent 4,088,448. Thus, according to the present invention, the measurement can ~e carried out by using different electrodes, the surfaces of which are pressed against the exterior surface of the semipermeable membrane. Furthermore, optical instruments may be used.
Within the scope of the present invention are also elec-trode or sensor systems integrated with, i.e. applied on or incorporated in, the semipermeable membrane material.
Another very important advantage as compared with the previously known cuvette is that the use ~, ~2~Z~CJl of membranes makes it possible to separate sample media from reagent media, and interferences originating from substances, unsuitable pH, unsuitable redox en-vironment etc. can be avoided. Thus, two or more reac-tion systems, which are incompatible, may be included in the new cuvette, as the semipermeable membrane acts as a barrier which prevents a component, e.g.
a reagent contained in the cavity from entering and disturbing the reaction(s) in the membrane(s), and vice versa. This second advantage makes the field of application for the present cuvette even broader and useful for a widè variety of different analyses.
Thus, the additional advantages according to the present invention emanate from the use of the semipermeable membrane and the possibility of combining this membrane with external or lnternal electrodes.
Analyses based on the use of semipermeable membranes and electrodes are known in the art. However, using known technique, difficulties are encountered in the handling of the sample, electrodes which often are sensitive to contamination, may be contaminated, evapo-ration of the sample may occur, and the sample may be subjected to the influence of different types of gases, such as the oxygen of the air. All these problems can be avoided by using the cuvette according to the present invention.
According to the present invention, the body member may consist of glass or polymeric material.

l~ZSZ7[31 It is also quite possible to make the whole body member or one wall thereof of the semipermeable material which in this case preferably should be self-supporting.
If not essentially self-supporting, the membrane could be used as a coating on the surface of the body member facing the cavity. The reagent, if any, coated on at least a portion of the body (body member) surface facing the cavity may be deposited by evaporation, freeze-drying, spraying or screen-printing, as known in the art.
The semipermeable membra~e may be in the form of one separate membrane layer or two or more separate layers joined to each other to form a composite mem-brane. The various reagents may be coated on the mem-brane surface facing the cavity and applied thereto by evaporation, freeze-drying, spraying or screen-printing, etc. It i5 also possible to have the reagents deposited as a layer on separate surfaces of the membrane in such a way that this layer becomes an intermediate layer in the finished composite membrane. One or more such layers may be present. The semipermeable membrane may also be prepared in such a manner that the reagent or reagents are dispersed or dissolved throughout the whole membrane or one or more layers thereof.
Another possibility is to prepare the membrane material in such a manner that the reagent molecules are covalent-ly bound to the polymer molecules of the semipermeable membrane.

/ J`
~.

~z~z~
The semipermeable membrane material is chosen in dependence on the kind of analysis to be performed and may be determined by a person skilled in the art.
The membrane material might be hydrophilic or hydrophobic.
Examples of different material which can be used accord-ing to the present invention are Teflon ~, silicon rubber, polyacrylates, polyvinyls, collagen and even crosslinked enzymes, etc.. Various substances could be incorporated in the membrane to give special selec-tive properties, to perform a chemical reaction, etc.
Including specific crown ethe~s in a polyvinyl membrane gives a membrane with selective properties for alkaline ions. Including glucose oxidase in a membrane makes it possible to measure glucose by the production of hydrogen peroxide or the decrease in oxygen concentra-tion.
The membrane may selectively permit penetration of only or essentially the substance/ion, which is relevant/interesting, and which can be detected by, for example, an electrode on the external surface of the membrane. Furthermore, the membrane may function as a discriminator in which only molecules~ions below a certain size can move freely.
To perform measurements with electrodes on or in the improved cuvette, the membrane acts as a semi-permeable barrier (with or without selective properties) which prevents the electrode from being contaminated by the sample medium and/or the reagent. The membrane ~ZSZ7~3~

could participate in a chemical reaction through incor-~ora,ed reagents and/or selectively permit free passage for the substances to be determined at the electrode.
The electrode to be used according to the present invention may be a conventional potentiometric, i.e.
ion-selective or amperometric electrode which, together with the semipermeable membrane of the cuvette, functions as an enzyme electrode or biosensor of the type described in e.g. P. Vadgama, Journal of Medical Engineering &
Technology, Vol. 5, No. 6, 1981, 293-298.
Examples of electrodes tO be used with the membrane cuvette of the present invention are conventional electrodes, such as a glass electrode (pH3, a platinum, gold, or carbon electrode, and other more exclusive electrodes, such as solid state devices of the type CHEMFET or ISFET with their associated electronic parts.
An example of a platinum/silver-silver chloride electrode system together with a composite membrane for determining glucose by amperometric measurement of consumed oxygen is given in a paper by Jean-Louis Romtte, B. Fromment ~ D. Thomas (Clin. Chim. Acta, 95 (1979) 249-253).
An example of glass electrode application together with a composite membrane for determining urea by pH-measurement of produced ammonia is disclosed in a paper by M. Mascini and G.G. Guilbault ~Anal. Chem.
Vol. 49, No. 6, May 1977, 795-798).

As regards optical analyses to be performed with the present cuvette, there are two main possibilities:
A) the colour develops in the cavity;
B) the colour develops within the membrane.
In A), the two main surfaces of the cavity must have a predetermined or a determinable distance between one another to make it possible to determine the optic~l path length. The determinahle distance may be obtained by applying an external orce to the surface of an essentially elastic membrane until the movement of the membrane is stopped against a spacer of predeter-mined thickness inserted in the cavity.
In B), the colour developing part (layer3 of the membrane or the entire membrane must be of a pre-determined thickness to accomplish a determined optical path length.
A practical example of B) is a cuvette designed to perform an analysis of urea in serum or urine.
The cavity contains urease and an alkaline buffer sytem in dry form which, when dissolved in the sample medium, give free ammonia from urea, and the membrane incorporates an indicator (= a reagent) for ammonia.
The membrane is manufactured from a polymer, the hydro-phobicity of which is sufficiently high to prevent the alkaline buffer from interfering with the indicator, but is permeable to ammonia. The indicator i~ a solvent soluble pH-indicator with an indicator interval within ~he acid range.

~ZS2~1 Different approaches to the analyses may ~e made by using different types of electrodes, different types of membranes and different reaction routes, as recognised by a person skilled in the art.
The invention will be described in more detail below, reference being had to the accompanying drawings which illustrate schematically and on a large scale a number of embodiments. In the drawings:
Fig. 1 shows a measuring cuvette according to the invention.
Fig. 2 shows a section on line I-I in Fig. l;
Fig. 2a shows a modified embodiment of the cuvette;
Fig. 2b shows a view of Fig. 2a;
Fig. 3 shows the cuvette according to Figs. 2 and 2a in contact with a measuring electrode;
Fig. 4 shows the cuvette according to Figs. 2 and 2a adapted for optical measurement;
Fig. 5 shows an embodiment in which the cuvette has parallel-connected cavities;
Fig. 5a shows a section on line II-II;
Fig. 6 shows a further modified embodiment of the cuvette;
Fig~ 6a shows a section on line III-III.
The cuvette illustrated in Figs. 1 and la comprises a body wall 10 of glass or polymeric material, and a body wall 11 of semipermeable membrane material. The walls define a cavity 12 which is intended to accommo-date a liquid sample and the dimension of which is 9 . , ~Z5~7q~)~

such that it can be filled by capillary force.`Two channels 13 extend from opposite sides of the cuvette and open into the cavity 12. Thus, a sample can here be drawn straight through the cuvette, which may be advantageous in certain cases. The cavity 12 might be supplied with a reagent (that is an agent to re~ct with the sample drawn into said cavity) by evaporation, freeze-drying, spraying, screen-printing or in another suitable manner according to the manner in which the cuvette is manufactured.
The wall 11 of semipermeable membrane material may be manufactured in such a manner that a reagent system is incorporated in the membrane, e.g. dispersed or dissolved therein. It is also possible to manufacture the membrane in such a way that the components (mole-cules) of the reagent system are covalently bound to the polymers constituting $he membrane material.
Another possibility is to build up a semipermeable membrane of two or more layers and apply the reagent system or systems as intermediate layers between two adjacent membrane layers. One or more such layers and intermediate layers may be present. All types of combinations of incorporation of the reagent system apparent to those skilled in the art fall within the scope of the present invention.
In Fig. 2a, 10 is a body wall of polymeric support-ing material. 11 is a semipermeable membrane optionally ~L2S;Z7~

composed of several layers. 12 is the cavity àccommo-dating the sample. Elevations 14 determine the optical path length. When the sample is drawn into the cavity 12, air is pressed out through the slit 15. The body wall 10 and the semipermeable membrane 11 are joined together (welded or glued) along the joint 16'. The area 17 indicates a suitable measuring zone.
In Fig. 3 a measuring electrode i5 brought into contact with the semipermeable membrane 11 in the cuvette disclosed in Figs. 2a and 2b. In this special embodiment, the electrode consists of a platinum elec-trode 18 and a reference silver/silver chlori~e elec-trode 19. 20 designates the glass body surrounding the platinum electrode 18.
In Fig. 4 the cuvette of the Figs. ~a and 2b is adapted for optical measuring. Thus, 21 here desig-nates a light source for e.g. monochromatic light.
22 indicates the light path towards the cuvette. 23 indicates the light path of unabsorbed light after the cuvette, and 24 is an optical detector.
The cuvette as shown in Fig. 5 has four parallel-connected cavities 25, 25' which are connected to a common channel 26 by branch channels 27 which continue on the oposite side of the cavities and open into the atmosphere to prevent air inclusions in the cavities when samples are drawn thereinto. Different reactive systems may be included in different cavities and/or the membrane material de~ining the whole or part of 'he cavity.

11 , 12~7~j~

Fig. 5a shows a section of the cuvette according to Fig. 5 along line II-II.
The embodiment of the present invention according to Figs. 6 and 6a consists of elastic semipermeable material. The inlet channel 28 communicates the exterior of the cuvette with the cavity 12 While the invention has been described with refe-rence to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made without depart-ing from the spirit and scope of the invention. Many alternative container designs can be conceived!which give the advantageous results herein disclosed.
Further, it is obvious that any analytical proce-dure can be adapted to the invention herein disclosed.
The cuvette is particularly suitable for routine blood chemistry, such as glucose, blood urea nitrogen, albumin, bilirubin, total protein, etc., and numerous other analytical tests.
Accordingly, all substitutions, additions and modifications to which the present invention is readily susceptible, without departing from the spirit and scope of this disclosure~ are considered part of the present invention.

Claims (12)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A disposable cuvette for simultaneously sampling a fluid and analyzing the sampled fluid, comprising:
a body member having an exterior and at least one cavity defined by surrounding walls, an inlet in said walls communicating said cavity with the exterior of the body member and through which said sampled fluid can enter said cavity by capillary forces, at least one of the walls including a semipermeable membrane, said semipermeable membrane having one surface defining a portion of said cavity and an opposite surface forming an external surface of said cuvette, said semipermeable membrane having a predetermined porosity and thereby functioning as a discriminator to permit entry only of molecules/ions up to a certain size, and at least one reagent incorporated in the cuvette in contact with said semipermeable membrane.
2. Cuvette according to claim 1, wherein said semipermeable membrane includes a polymeric material, and molecules of the at least one reagent are covalently bound to the polymers of the semipermeable membrane.
3. Cuvette according to claim 1, wherein said at least one reagent is coated on at least a portion of a surface of said semipermeable membrane facing the cavity.
4. Cuvette according to claim 1, wherein said surrounding walls of said cavity are defined by two spaced planar surfaces, and said two planar surfaces of the cavity define an optical path length.
5. Cuvette according to claim 1, wherein the semipermeable membrane has a predetermined fixed thickness defining an optical path length.
6. Cuvette according to claim 1, further including sensor means applied on the semipermeable membrane for analyzing a sampled fluid.
7. Cuvette according to claim 1, further including sensor means incorporated in the semipermeable membrane for analyzing a sampled fluid.
8. Cuvette according to claim 1, wherein the semipermeable membrane comprises at least one membrane layer.
9. Cuvette according to claim 8, wherein at least one reagent is in contact with at least one membrane layer of the semipermeable membrane.
10. Cuvette according to claim 9, wherein said at least one reagent is dispersed in at least one layer of said semipermeable membrane.
11. Cuvette according to claim 9, wherein said at least one reagent is dissolved in at least one layer of said semipermeable membrane.
12. Cuvette according to claim 9, wherein said at least one regeant is located on said semipermeable membrane.
CA000465095A 1983-10-18 1984-10-10 Cuvette Expired CA1252701A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE8305704-2 1983-10-18
SE8305704A SE8305704D0 (en) 1983-10-18 1983-10-18 Cuvette

Publications (1)

Publication Number Publication Date
CA1252701A true CA1252701A (en) 1989-04-18

Family

ID=20352930

Family Applications (1)

Application Number Title Priority Date Filing Date
CA000465095A Expired CA1252701A (en) 1983-10-18 1984-10-10 Cuvette

Country Status (9)

Country Link
US (1) US4654197A (en)
EP (1) EP0138152B1 (en)
JP (1) JPS60100742A (en)
CA (1) CA1252701A (en)
DE (1) DE3475834D1 (en)
DK (1) DK160221C (en)
FI (1) FI81677C (en)
NO (1) NO162833C (en)
SE (1) SE8305704D0 (en)

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