EP0792459A1 - Analytical method for saliva - Google Patents

Analytical method for saliva

Info

Publication number
EP0792459A1
EP0792459A1 EP95936683A EP95936683A EP0792459A1 EP 0792459 A1 EP0792459 A1 EP 0792459A1 EP 95936683 A EP95936683 A EP 95936683A EP 95936683 A EP95936683 A EP 95936683A EP 0792459 A1 EP0792459 A1 EP 0792459A1
Authority
EP
European Patent Office
Prior art keywords
saliva
properties
kit
flow
altering
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.)
Withdrawn
Application number
EP95936683A
Other languages
German (de)
French (fr)
Inventor
Keith Peek
Christopher John Smith
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.)
Cortecs Ltd
Original Assignee
Cortecs Ltd
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
Application filed by Cortecs Ltd filed Critical Cortecs Ltd
Publication of EP0792459A1 publication Critical patent/EP0792459A1/en
Withdrawn legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56911—Bacteria
    • G01N33/56922—Campylobacter

Definitions

  • This invention relates to a method of treating saliva.
  • it relates to a method of treating saliva for use in a diagnostic test for the presence of antigens to H. pylori .
  • Saliva is a complex mixture of secretions originating from various glands within the oral cavity. Among its many constituents are various enzymes, immunoglobulins and mucins, together with cellular debris and a host of bacterial flora.
  • the mucins are responsible for the viscoelastic properties of saliva, and act as lubricants with protective and antibacterial properties.
  • the viscoelastic properties of these glycoproteins depend on the protein and carbohydrate composition acquired during synthesi's, but are also influenced by the extent of their interaction with other components of saliva. For example, lipids can also contribute significantly to the viscoelastic properties of saliva.
  • Saliva which contains immunoglobulins can be used for the diagnosis of various diseases.
  • the detection of IgG specific to antigens produced by pathogens is indicative of infection or recent contact.
  • One example of such an infection is that caused by H. pylori .
  • the diagnosis of H. pylori infection can be made by microscopy, microbiological culture or urease detection in gastric mucosal biopsies, urea breath test or by the presence of specific antibodies in serum detected by ELISAs.
  • H. pylori infects the gastric mucosa and would be expected to elicit an IgA antibody response that could be detected in mucous in gastric secretions.
  • the predominant H is the predominant H.
  • pylori -specific antibody found in mucous secretions is IgG class and not IgA.
  • AU-A-9067676 describes a method for the detection of IgG in mucous secretion specific to H. pylori antigen, thereby providing a means of monitoring infection by that microorganism in mammals.
  • the corresponding academic publication is Witt et al , Frontiers in Mucosal Immunology 1 693-696 (1991) .
  • WO-A-9322682 discloses a convenient and reliable in vi tro test for H. pylori . This test utilises an antigen preparation that reacts with. IgG antibody in a mucous secretion from a mammal being tested.
  • Particulates which are present in saliva can bind to the membrane, by simple deposition on the surface and reduce flow times.
  • the mucins have viscoelastic properties and this can result in a gel-like matrix being deposited on the membrane which will reduce liquid flow.
  • the flow- through time of the saliva must be a balance between the need for accurate binding of IgG to antigen, which means that the flow-through time must not be too fast, and the need for the test to be practical, i.e. the flow-through time must not be too slow.
  • the binding of particulates and mucins to the surface of any membrane or pad to which the antigen is bound can lead to greatly reduced flow- through time.
  • a further problem associated with deposition of mucins and particulates on the membrane is related to signal development.
  • One preferred method of signal development utilises IgG-Colloidal Gold conjugates which can be trapped by the deposits. This, can lead to false positive results, and in a worst case, where no conjugate can pass freely, the whole membrane can bind conjugate.
  • saliva can be processed using a system known as Omnisal ® in which saliva is collected onto a cotton pad then extracted in a buffer and filtered through a porous plastic filter.
  • Omnisal ® a system known as Omnisal ® in which saliva is collected onto a cotton pad then extracted in a buffer and filtered through a porous plastic filter.
  • the liquid so produced can still have poor flow characteristics.
  • the present invention provides a method of improving the flow characteristics of saliva, which comprises the step of altering the properties of the saliva sample.
  • the invention relates to altering the viscoelastic properties of the saliva.
  • the properties of the saliva are altered by passing the saliva through a filtration medium which achieves this effect.
  • Preferred filtration media include charcoal, DEAE-sepharose and diatomaceous earth, e.g. Celite ® , with diatomaceous earth being particularly preferred.
  • the filtration medium removes particulates. Mechanical shear, removal of high molecular weight aggregates and lipids may disrupt the polymeric structure of mucins, leading to improved flow characteristics.
  • Mucins present are not removed by the method, however, their polymeric structure may be altered, thus improving flow characteristics.
  • the properties of the saliva sample can be manipulated by the addition of detergents and adjusting the ionic strength and/or pH of the saliva sample. This can be achieved by passing the saliva sample into a suitable buffer solution.
  • a suitable buffer solution e.g., a suitable buffer solution
  • the saliva sample is not only passed through a filtration medium which alters the properties of the saliva, but also has its pH and/or ionic strength adjusted and detergent added by means of passing into a suitable buffer solution.
  • the present invention finds particular application in rapid diagnostic tests for specific antibodies found in saliva. Therefore, in a further aspect, the present invention provides a method for the detection of an antibody in a sample of saliva which comprises the step of altering the properties, e.g. the viscoelastic properties, of the saliva to improve flow characteristics. As described herein, this can be achieved by means of filtration and/or buffer manipulation.
  • the test is for the detection of H. pylori specific antibody, usually IgG.
  • the present invention provides a kit for the detection of an antibody in a sample of saliva which comprises a means for altering the properties, e.g. the viscoelastic properties, of the saliva sample, those means being provided in the form of a filtration material and/or a buffer solution, either or both of which have the ability to alter the flow properties of the saliva sample before application to the test area.
  • a means for altering the properties e.g. the viscoelastic properties
  • Fi ⁇ ure 1 shows saliva flow times with or without a Celite ® filtration step
  • Fi ⁇ ure 2 shows IgG Gold conjugate flow times with or without a Celite ® filtration step.
  • Saliva samples were collected from a number of individuals using the Omnisal ® (Saliva Diagnostic Systems, Inc., 11719 NE 95th Street, Vancouver, WA 98682, USA) saliva collection and processing system. However, the saliva was extracted into the following buffer: 20 mM Phosphate pH 7.0-8.0 containing 0.5% v/v Tween 60, 125 mM NaCl, 10 mM Sodium azide and 0.1% w/w BSA.
  • the saliva was either extracted into the buffer by filtering through the Omnisal ® filter or through Celite ® . 1 ml of the resulting solutions were then placed onto a Helisal ® rapid test card, which contains membrane spotted with antigen, and the flow through times recorded. After saliva, 1 ml of IgG-gold conjugate was added and the flow through time also recorded. The results are shown below.
  • FIGS. 1 and 2 are a representation of the above data graphically. The following points are clear:
  • Samples processed as described above also show a significant reduction in background colour due to trapping of IgG-Gold, and the number of false positives is greatly reduced.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Biochemistry (AREA)
  • Cell Biology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Biotechnology (AREA)
  • Food Science & Technology (AREA)
  • Virology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Microbiology (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Peptides Or Proteins (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)

Abstract

A method of improving the flow characteristics of saliva, which comprises the step of altering the properties of the saliva. Preferably, the method involves a filtration step and/or altering the pH/ionic strength of the saliva, as well as the addition of detergent.

Description

ANALYTICAL METHOD FOR SALIVA
This invention relates to a method of treating saliva. In particular, it relates to a method of treating saliva for use in a diagnostic test for the presence of antigens to H. pylori .
Saliva is a complex mixture of secretions originating from various glands within the oral cavity. Among its many constituents are various enzymes, immunoglobulins and mucins, together with cellular debris and a host of bacterial flora. The mucins, in particular, are responsible for the viscoelastic properties of saliva, and act as lubricants with protective and antibacterial properties. The viscoelastic properties of these glycoproteins depend on the protein and carbohydrate composition acquired during synthesi's, but are also influenced by the extent of their interaction with other components of saliva. For example, lipids can also contribute significantly to the viscoelastic properties of saliva.
Saliva which contains immunoglobulins can be used for the diagnosis of various diseases. In particular, the detection of IgG specific to antigens produced by pathogens is indicative of infection or recent contact. One example of such an infection is that caused by H. pylori . The diagnosis of H. pylori infection can be made by microscopy, microbiological culture or urease detection in gastric mucosal biopsies, urea breath test or by the presence of specific antibodies in serum detected by ELISAs. H. pylori infects the gastric mucosa and would be expected to elicit an IgA antibody response that could be detected in mucous in gastric secretions. However, it has been discovered that the predominant H. pylori -specific antibody found in mucous secretions is IgG class and not IgA. AU-A-9067676 describes a method for the detection of IgG in mucous secretion specific to H. pylori antigen, thereby providing a means of monitoring infection by that microorganism in mammals. The corresponding academic publication is Witt et al , Frontiers in Mucosal Immunology 1 693-696 (1991) .
The presence of IgG antibodies in the saliva of H. pylori { Campylobacter pylori) positive patients has received some attention in the proceedings of the Annual Meetings of the American Gastroenterological Association. After the disclosure by Czinn et al of the presence of such antibodies in the 1989 proceedings, Larsen et al concluded in the May 1991 proceedings that salivary IgG levels are a practical, non-invasive marker of therapeutic response during a course of antibiotic therapy. In the April 1992 proceedings, andes et al confirmed earlier observations and observed that measurement of salivary IgG to HelicoJbacter pylori is a simple, non-invasive test for detecting H. pylori positive patients, especially in widespread or paediatric populations where other tests are not practical.
WO-A-9322682 discloses a convenient and reliable in vi tro test for H. pylori . This test utilises an antigen preparation that reacts with. IgG antibody in a mucous secretion from a mammal being tested.
However, the use of saliva in such diagnostic methods also has its attendant problems. These methods of diagnosis often rely on contacting the saliva sample with antigen bound to a membrane or pad, or other similar material. Flow-through of the saliva on such a device is therefore an essential element of the test. Also, predictable flow-through times are essential to provide accurate and meaningful results. However, because of the complex nature of saliva, and in particular the presence of particulates and mucins, the flow-through properties of individual saliva samples are subject to both extensive intra and inter subject variability.
Particulates which are present in saliva can bind to the membrane, by simple deposition on the surface and reduce flow times. The mucins have viscoelastic properties and this can result in a gel-like matrix being deposited on the membrane which will reduce liquid flow. The flow- through time of the saliva must be a balance between the need for accurate binding of IgG to antigen, which means that the flow-through time must not be too fast, and the need for the test to be practical, i.e. the flow-through time must not be too slow. The binding of particulates and mucins to the surface of any membrane or pad to which the antigen is bound can lead to greatly reduced flow- through time.
A further problem associated with deposition of mucins and particulates on the membrane is related to signal development. One preferred method of signal development utilises IgG-Colloidal Gold conjugates which can be trapped by the deposits. This, can lead to false positive results, and in a worst case, where no conjugate can pass freely, the whole membrane can bind conjugate.
Theoretically, it is possible to remove mucins. However, the reagents and solid-phase media required do not make such an approach commercially acceptable. Thus, an alternative, more economical way is needed to reduce deposition and hence improve flow- hrough times.
Currently, saliva can be processed using a system known as Omnisal® in which saliva is collected onto a cotton pad then extracted in a buffer and filtered through a porous plastic filter. However, the liquid so produced can still have poor flow characteristics.
It has now surprisingly been found that by altering the properties, e.g. the viscoelastic properties, of the saliva sample, flow-through times can be improved, leading to a more accurate and sensitive test. This does not require removal of, for instance, the mucins present in the saliva, only an alteration of their properties.
Thus, the present invention provides a method of improving the flow characteristics of saliva, which comprises the step of altering the properties of the saliva sample. In particular, the invention relates to altering the viscoelastic properties of the saliva.
In a preferred embodiment of the invention, the properties of the saliva are altered by passing the saliva through a filtration medium which achieves this effect. Preferred filtration media include charcoal, DEAE-sepharose and diatomaceous earth, e.g. Celite®, with diatomaceous earth being particularly preferred. The filtration medium removes particulates. Mechanical shear, removal of high molecular weight aggregates and lipids may disrupt the polymeric structure of mucins, leading to improved flow characteristics.
Mucins present are not removed by the method, however, their polymeric structure may be altered, thus improving flow characteristics.
In a second embodiment of the invention, the properties of the saliva sample can be manipulated by the addition of detergents and adjusting the ionic strength and/or pH of the saliva sample. This can be achieved by passing the saliva sample into a suitable buffer solution. Of course, if the properties of the saliva are adjusted in this way, it is also usual to include a separate filtration step to remove particulate matter.
Thus, in a particularly preferred embodiment of the invention, the saliva sample is not only passed through a filtration medium which alters the properties of the saliva, but also has its pH and/or ionic strength adjusted and detergent added by means of passing into a suitable buffer solution.
The method of the present invention finds particular application in rapid diagnostic tests for specific antibodies found in saliva. Therefore, in a further aspect, the present invention provides a method for the detection of an antibody in a sample of saliva which comprises the step of altering the properties, e.g. the viscoelastic properties, of the saliva to improve flow characteristics. As described herein, this can be achieved by means of filtration and/or buffer manipulation.
Preferably the test is for the detection of H. pylori specific antibody, usually IgG.
Such diagnostic methods are usually carried out using a diagnostic kit comprising a membrane or pad to which the antigen is bound. In yet a further aspect, therefore, the present invention provides a kit for the detection of an antibody in a sample of saliva which comprises a means for altering the properties, e.g. the viscoelastic properties, of the saliva sample, those means being provided in the form of a filtration material and/or a buffer solution, either or both of which have the ability to alter the flow properties of the saliva sample before application to the test area.
The invention will now be described with reference to the following example, which should not be construed as in any way limiting the invention.
The example refers to the figures in which:
Fiσure 1: shows saliva flow times with or without a Celite® filtration step;
Fiσure 2: shows IgG Gold conjugate flow times with or without a Celite® filtration step.
EXAMPLE
Saliva samples were collected from a number of individuals using the Omnisal® (Saliva Diagnostic Systems, Inc., 11719 NE 95th Street, Vancouver, WA 98682, USA) saliva collection and processing system. However, the saliva was extracted into the following buffer: 20 mM Phosphate pH 7.0-8.0 containing 0.5% v/v Tween 60, 125 mM NaCl, 10 mM Sodium azide and 0.1% w/w BSA.
The saliva was either extracted into the buffer by filtering through the Omnisal® filter or through Celite®. 1 ml of the resulting solutions were then placed onto a Helisal® rapid test card, which contains membrane spotted with antigen, and the flow through times recorded. After saliva, 1 ml of IgG-gold conjugate was added and the flow through time also recorded. The results are shown below.
RESULTS
DISCUSSION
Figures 1 and 2 are a representation of the above data graphically. The following points are clear:
i) flow times of both the saliva samples themselves and the IgG-Gold conjugates are reduced as a result of the processing steps,*
ii) in addition, the flow times in both cases show much less variation between samples.
Samples processed as described above also show a significant reduction in background colour due to trapping of IgG-Gold, and the number of false positives is greatly reduced.

Claims

1. A method of improving the flow characteristics of saliva, which comprises the step of altering the properties of the saliva.
2. A method as claimed in claim 1 wherein the viscoelastic properties of the saliva are altered.
3. A method as claimed in claim 1 or claim 2 wherein the properties of the saliva are altered by passing the saliva through a filtration medium.
4. A method as claimed in claim 3 wherein the filtration medium is charcoal, DEAE-sepharose or diatomaceous earth.
5. A method as claimed in claim 4 wherein the filtration medium is Celite®.
6. A method of improving the flow characteristics of saliva which comprises the step of manipulating the pH and/or ionic strength of the saliva and adding detergen .
7. A method as claimed in claim 6 wherein the saliva sample is also subjected to a filtration step as defined in any one of claims 3 to 5.
8. A method for the detection of an antibody in a sample of saliva which comprises the step of altering the properties of the saliva to improve its flow characteristics.
9. A method as claimed in claim 8 modified by any one or more of the features of claims 2 to 7.
10. A method as claimed in claim 9 wherein the antibody is H. pylori specific antibody.
11. A method as claimed in claim 10 wherein the H. pylori specific antibody is IgG.
12. A kit for the detection of an antibody in a sample of saliva which comprises a means for altering the properties of the saliva to improve its flow characteristics.
13. A kit as claimed in claim 12 wherein the means comprises a filtration medium.
14. A kit as claimed in claim 13 wherein the filtration medium is diatomaceous earth.
15. A kit as claimed in claim 14 wherein the diatomaceous earth is Celite®.
16. A kit as claimed in any one of claims 12 to 15 wherein the kit further comprises a buffer and/or detergent.
EP95936683A 1994-11-15 1995-11-14 Analytical method for saliva Withdrawn EP0792459A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB9422991A GB9422991D0 (en) 1994-11-15 1994-11-15 Analytical method
GB9422991 1994-11-15
PCT/GB1995/002668 WO1996015455A1 (en) 1994-11-15 1995-11-14 Analytical method for saliva

Publications (1)

Publication Number Publication Date
EP0792459A1 true EP0792459A1 (en) 1997-09-03

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
EP95936683A Withdrawn EP0792459A1 (en) 1994-11-15 1995-11-14 Analytical method for saliva

Country Status (13)

Country Link
EP (1) EP0792459A1 (en)
JP (1) JPH10508689A (en)
AU (1) AU3852995A (en)
BR (1) BR9509677A (en)
CA (1) CA2205088A1 (en)
FI (1) FI972055A0 (en)
GB (1) GB9422991D0 (en)
IL (1) IL116009A0 (en)
MX (1) MX9703563A (en)
NO (1) NO972221L (en)
TW (1) TW340183B (en)
WO (1) WO1996015455A1 (en)
ZA (1) ZA959731B (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0985875A3 (en) * 1998-09-08 2002-03-06 Ushiodenki Kabushiki Kaisha Light source device

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4651868B2 (en) * 2001-03-28 2011-03-16 株式会社ジーシー Saliva pretreatment kit and saliva pretreatment method using the same
JP4642277B2 (en) * 2001-06-21 2011-03-02 株式会社ジーシー Saliva pretreatment tool and saliva pretreatment method
US7001717B2 (en) * 2003-12-05 2006-02-21 Biofx Laboratories, Inc. Charcoal stabilization of phenyl phosphates
US20130217034A1 (en) * 2010-08-13 2013-08-22 Dentognostics Gmbh Process for avoiding false positive results in a detecting process of an inflammation indicator in a rinse solution for taking up gingival crevicular fluid
KR101716729B1 (en) * 2016-09-27 2017-03-27 주식회사 토브스 Apparatus and method for analyzing saliva and system and method for monitoring animal using the apparatus

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4053363A (en) * 1976-06-28 1977-10-11 J. K. And Susie L. Wadley Research Institute And Blood Bank Sputum analysis method
US4424216A (en) * 1979-07-31 1984-01-03 The Rockefeller University Method for the reduction of mucin viscosity
CA1317860C (en) * 1987-04-01 1993-05-18 Daniel Louis Kacian Techniques for preparing specimens for bacterial assays
US5459041A (en) * 1988-02-18 1995-10-17 Enteric Research Laboratories, Inc. Campylobacter pylori antigens and uses thereof for detection of Campylobacter pylori infection
US5112758A (en) * 1988-05-09 1992-05-12 Epitope, Inc. Treating body fluids for diagnostic testing
JPH01291160A (en) * 1988-05-18 1989-11-22 Kyokuto Seiyaku Kogyo Kk Implement for expectoriation treatment

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9615455A1 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0985875A3 (en) * 1998-09-08 2002-03-06 Ushiodenki Kabushiki Kaisha Light source device

Also Published As

Publication number Publication date
FI972055A (en) 1997-05-14
NO972221D0 (en) 1997-05-14
AU3852995A (en) 1996-06-06
GB9422991D0 (en) 1995-01-04
ZA959731B (en) 1997-05-15
FI972055A0 (en) 1997-05-14
CA2205088A1 (en) 1996-05-23
WO1996015455A1 (en) 1996-05-23
BR9509677A (en) 1997-09-16
JPH10508689A (en) 1998-08-25
MX9703563A (en) 1997-08-30
IL116009A0 (en) 1997-08-14
NO972221L (en) 1997-05-14
TW340183B (en) 1998-09-11

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