WO1987001120A1 - Method of attaching biological substances to solid substrates - Google Patents

Method of attaching biological substances to solid substrates Download PDF

Info

Publication number
WO1987001120A1
WO1987001120A1 PCT/AU1986/000235 AU8600235W WO8701120A1 WO 1987001120 A1 WO1987001120 A1 WO 1987001120A1 AU 8600235 W AU8600235 W AU 8600235W WO 8701120 A1 WO8701120 A1 WO 8701120A1
Authority
WO
WIPO (PCT)
Prior art keywords
solid
biological substance
substrate
group
attachment
Prior art date
Application number
PCT/AU1986/000235
Other languages
French (fr)
Inventor
Dinesh Kumar Sood
Ralph Edward Blandford Green
Original Assignee
Royal Melbourne Institute Of Technology Limited
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 Royal Melbourne Institute Of Technology Limited filed Critical Royal Melbourne Institute Of Technology Limited
Priority to BR8606830A priority Critical patent/BR8606830A/en
Priority to HU864075A priority patent/HUT43092A/en
Publication of WO1987001120A1 publication Critical patent/WO1987001120A1/en
Priority to FI871599A priority patent/FI871599A0/en
Priority to DK200387A priority patent/DK200387D0/en

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
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/544—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being organic
    • G01N33/545—Synthetic resin
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C59/00—Surface shaping of articles, e.g. embossing; Apparatus therefor
    • B29C59/16—Surface shaping of articles, e.g. embossing; Apparatus therefor by wave energy or particle radiation, e.g. infrared heating
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N11/00—Carrier-bound or immobilised enzymes; Carrier-bound or immobilised microbial cells; Preparation thereof
    • 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
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/544—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being organic
    • G01N33/548—Carbohydrates, e.g. dextran
    • 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
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/551—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being inorganic
    • G01N33/552—Glass or silica
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C35/00—Heating, cooling or curing, e.g. crosslinking or vulcanising; Apparatus therefor
    • B29C35/02—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould
    • B29C35/08—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation
    • B29C35/0866—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation using particle radiation
    • B29C2035/0872—Heating or curing, e.g. crosslinking or vulcanizing during moulding, e.g. in a mould by wave energy or particle radiation using particle radiation using ion-radiation, e.g. alpha-rays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29L—INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES
    • B29L2031/00—Other particular articles
    • B29L2031/753—Medical equipment; Accessories therefor

Definitions

  • Support materials used have included cellulose, agarose, dextran, polyacrylamide, glass, rubber and plastics including nylon, polystyrene and polyesters etc. Direct chemical bonding to produce covalent attachment may be used.
  • Chemical methods of attaching either an antigen or an antibody to the support material include the use of linking agents such as glutaraldehyde, cyanogen bromide, carbodiimides and aminoalkylsilanes. These techniques are well known to those skilled in the art.
  • Attachment of antigens or antibodies to plastic surfaces may be achieved by direct adsorption. This is a simple method of attachment however it has several disadvantages.
  • the adsorption of the antigen or antibody to the surface is achieved by hydrophobic interaction and van der aals forces. These are relatively weak attractive forces and as a result the attached material may elute from the surface during subsequent handling of the solid support (1) .
  • soluble materials such as antibodies and antigens
  • Attachment may be facilitated using techniques known to those skilled in the art (4) . These techniques generally involve pre-treatment of the solid support with agents such as glutaraldehyde, poly-L-lysine, phenylalaninelysine copolymer or lectins derived from sources such as Glycine max, Limulus polyphemus, Lens culinaris and Phaseolus vulgaris, etc.
  • Cells may also be attached to a solid support by first attaching to the support an antibody which is specific for the cell. Attachment of the antibody may be achieved by the techniques previously mentioned.
  • the biological substance is then brought into contact with the treated substrate.
  • the unique bonding process of the present invention may be conducted at room temperature and does not require any extraneous chemical bonding agents. In this respect,
  • the method of the present invention is utilised to attach red blood cell membranes to transparent plastic solid-phase substrates chosen as test substrates, the first being polypropylene (which possesses no reactive groups) , and the second being Mylar (which has some reactive groups) .
  • red blood cell membranes in colloidal suspension in a suitable liquid are then injected in situ (in vacuum) onto the surface which has been treated by ion bombardment.
  • the liquid quickly spreads to a fine coating with the red blood cell membranes being bonded so strongly to the substrate surface that even extended ultrasonic treatment in water has no effect in removal of the membranes from the surface.
  • Sepharose-Staph A affinity column chromatography. An aliquot of the purified IgG was radiolabelled with 125I by the Chloramine T method. Radiolabelled IgG was added to the purified IgG as a tracer to give a ratio of labelled to unlabelled IgG of between 1:20 and 1:30.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • General Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • Medicinal Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Cell Biology (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Organic Chemistry (AREA)
  • Toxicology (AREA)
  • General Engineering & Computer Science (AREA)
  • Inorganic Chemistry (AREA)
  • Treatments Of Macromolecular Shaped Articles (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

A method of attaching a biological substance to a solid-phase substrate for use, for example, in solid-phase immunoassays, comprises the steps of: (i) subjecting the solid-phase substrate to ion bombardment, and (ii) contacting the treated substrate with a biological substance to be attached thereto.

Description

METHOD OF ATTACHING BIOLOGICAL SUBSTANCES TO SOLID SUBSTRATES
This invention relates to a method of attaching biological substances to solid substrates, and relates particularly, but not exclusively, to the attachment of biological materials such as antigens and/or antibodies to solid-phase substrates for use in . solid-phase immunoassays. The invention also relates to the products which are produced by using the said method.
The attachment of one of the partners in an immunological reaction to a solid support facilitates the qualitative and/or quantitative measurement of the reaction. Generally the immobilization of one of the partners allows for easy separation of the reaction products from unreacted components. In effect the immobilised partner in the reaction captures its complementary reactant from solutions and binds it to a solid-phase. Once bound to this solid-phase its presence may then be measured either quantitatively or qualitatively.
In the past, the immobilisation of one of the partners in an immunological reaction has been achieved by a number of different methods. Support materials used have included cellulose, agarose, dextran, polyacrylamide, glass, rubber and plastics including nylon, polystyrene and polyesters etc. Direct chemical bonding to produce covalent attachment may be used. Chemical methods of attaching either an antigen or an antibody to the support material include the use of linking agents such as glutaraldehyde, cyanogen bromide, carbodiimides and aminoalkylsilanes. These techniques are well known to those skilled in the art.
Attachment of antigens or antibodies to plastic surfaces may be achieved by direct adsorption. This is a simple method of attachment however it has several disadvantages. The adsorption of the antigen or antibody to the surface is achieved by hydrophobic interaction and van der aals forces. These are relatively weak attractive forces and as a result the attached material may elute from the surface during subsequent handling of the solid support (1) .
With solid supports such as microtitre plates, the efficiency of attachment of different antigens may vary dependent on their biochemical composition.
Additionally, antigen attachment to such plates may be highly variable between different wells on the same plate (2) .
Techniques to overcome these problems have involved pre-activation of the plastic surface. Two chemical methods of preactivation are disclosed in
European patent No. 83111144 and European Patent No. 84103367. These methods involve preactivation with phenylalaninelysine copolymer and diphenylene-bis- diazonium compounds respectively. A physical method of activating plastic microtitre plates is described in European Patent No. 82102257. This method entails the exposure of the microtitre plates to γ-rays. Gamma irradiation produces better attachment (and also sterilization) due to ionization effects leading to the presence of some free radicals/bonds (3) .
In addition to soluble materials such as antibodies and antigens, it may also be necessary to immobilise whole cells or cell extracts for use in immunological or biological reaction systems. Attachment may be facilitated using techniques known to those skilled in the art (4) . These techniques generally involve pre-treatment of the solid support with agents such as glutaraldehyde, poly-L-lysine, phenylalaninelysine copolymer or lectins derived from sources such as Glycine max, Limulus polyphemus, Lens culinaris and Phaseolus vulgaris, etc. Cells may also be attached to a solid support by first attaching to the support an antibody which is specific for the cell. Attachment of the antibody may be achieved by the techniques previously mentioned.
All of the attachment techniques mentioned above rely on the presence of reactive groups on the substrate. If not involved in the bonding process, such reactive groups need to be neutralised before the bonded antigen, antibody, cells or the like are used in immunoassays because they can allow the non-specific attachment of other material which is used in later steps of the immunoassay procedure. This non-specific attachment of material can lead to high background readings thus limiting the sensitivity of the test procedure. The biochemistry of the biological material will also determine which particular bonding process may be used, therefore there has been no universally applicable bonding technique which can effectively bond all types of biological materials to a particular substrate.
It has now been discovered that the attachment of biological substances to solid-phase substrates can be achieved by use of the technique of ion beam bombardment.
According to the present invention, there is provided a method of attaching a biological substance to a solid-phase substrate which comprises the steps of:- (i) subjecting a solid-phase substrate to ion bombardment, and (ii) contacting the treated substrate with a biological substance to be attached thereto.
The present invention also provides a product produced by the method described above. In this aspect, the invention includes a solid-phase product comprising a solid-phase substrate, the surface of which has been treated by ion bombardment, and a biological substance attached to said treated surface.
Suitable biological materials for use in accordance with the present invention include protein materials such as antigens, antibodies, immunoglobulins such as IgG, IgM and IgE, and enzymes, as well as cellular material such as red blood cell membranes, whole cells such as bacteria and viruses, and hormones such as thyroid stimulating hormone (TSH) . Suitable solid-phase substrates include in particular, but not exclusively, plastics materials such as polypropylene. Mylar, polystyrene, latex and Teflon; glass and silica; and cellulose and cellulose derivatives.
It has been found that the use of the ion beam bombardment technique enables specific bonding of biological substances to the solid-phase substrates with high affinity, stability and reproducibility.
The technique of ion beam bombardment is generally well known (5) , although it has not previously been used in the pretreatment of substrates for the attachment of biological substances. By way of example, U.S. Patents Nos. 3,682,729, 4,256,780 and 4,457,972 all illustrate the use of ion bombardment in the formation or deposition of films of metals and similar materials on substrates (See also Bodβ and Sundgren (6)). These prior disclosures do not, however, contain any reference whatsoever to the use of this technique in the attachment of biological substances to substrates.
The step of ion bombardment of the solid-phase substrate may, for example, be carried out by bombarding the substrate with a beam of energetic Ar ions. Whilst the exact mechanism which leads to the strong specific attachment of biological substances to such a treated substrate is not well understood at present, it is believed that ion bombardment could produce one or more of the following effects which are conducive to strong bonding at the interface:
(a) removal of surface impurities by sputtering;
(b) of etastable chemical "dangling" bonds which attach to the biological material; and (c) modification of surface composition by preferential sputtering.
The effects of ion bombardment are quite unique as compared to the well known interaction of milder ionizing radiation (γ-rays. X-rays, high energy electrons, pile irradiation, etc.) with polymer materials (7) . Since ion bombardment produces a much higher ionization density (stopping power) and can also produce atomic recoils, it is capable of generating metastable chemical surface states/compositions not attainable by milder forms of ionizing radiation or by any conventional equilibrium chemistry. In this sense, the ion bombardment technique is believed to be quite unique in that, it can not only produce effects similar to those generated by milder ionizing radiation, but also can produce many new metastable chemical states (dangling bonds) . This feature is believed to be responsible for more universal success of ion bombardment in producing enhanced attachment of many different types of biological materials to several different types of plastics.
Since the technique of ion beam bombardment is known, the performance of this step in the method of the present invention may be accomplished by use of any standard apparatus (5) .
Following bombardment of the solid-phase substrate material, the biological substance is then brought into contact with the treated substrate. The unique bonding process of the present invention may be conducted at room temperature and does not require any extraneous chemical bonding agents. In this respect,
Figure imgf000009_0001
there is thus provided a direct bonding between the biological substance and the treated substrate material, and furthermore, the biological material is not degraded or destroyed in any way since it is not irradiated or chemically treated during the attachment process.
In one particular embodiment of the present invention, to be described in greater detail below, the method of the present invention is utilised to attach red blood cell membranes to transparent plastic solid-phase substrates chosen as test substrates, the first being polypropylene (which possesses no reactive groups) , and the second being Mylar (which has some reactive groups) . Following bombardment of the plastic substrates with an energetic Ar+ ion beam, red blood cell membranes in colloidal suspension in a suitable liquid are then injected in situ (in vacuum) onto the surface which has been treated by ion bombardment. The liquid quickly spreads to a fine coating with the red blood cell membranes being bonded so strongly to the substrate surface that even extended ultrasonic treatment in water has no effect in removal of the membranes from the surface.
Further features of the present invention will be apparent from the following Examples which illustrate, but in no way limit, the present invention. In these Examples, small strips (1cm x 1.5cm) of polypropylene. Teflon, polystyrene and Mylar were cleaned with trichlorethylene, followed by rinses in methanol and air dried. Samples were then mounted in an ion bombardment chamber (Figure 1) which was evacuated to a pressure <lxlO -5 Torr. Samples were bombarded with
60keV Ar or He ions in the dose range of 5x10 to 5x1016 ions/cm2. The rectangular strip samples were bombarded over half the area and were used for the red blood cell experiment described in Example 1. Circular discs were over the entire area and were used for experiments described in other Examples. Several bombardment parameters studied in detail were ion dose, dose rate, ion species and ambient storage environment after bombardment (till the biological substance is brought in contact) . Extensive reproducibility checks were made.
EXAMPLE 1
A. Preparation of Red Blood Cell Membranes
Red blood cell membranes were prepared from fresh anticoagulated blood by the process of calcium phosphate cosedimentation (8) . Sodium azide was incorporated at a final concentration of 0.1% to inhibit bacterial contamination during the processing of the sample for attachment to the plastic substrate surface.
B. Attachment of Membranes to Substrates
Polypropylene strips were treated with Ar ions in apparatus illustrated in Figure 1. The strips were placed in sample holder 11 within the target chamber 10 with the system maintained totally under vacuum, and bboommbbaarrddeedd with accelerated Ar ions 12 through aperture plate 13.
Following ion bombardment of the strips, the sample holder 11 was transferred through air lock valve 20 to an adjacent air lock 21 without breaking vacuum (Figure 1). In air lock 21, a controlled volume of the red blood cell membrane calcium phosphate suspension was then injected onto the plastic strips through biological material injection port 22. The liquid did not wet the unbombarded regions of the polypropylene and quickly spread to produce a coating on the bombarded regions. The plastic strips were removed from the air lock and excess liquid removed. After allowing to air dry the strength of adhesion of the red cell membrane/calcium phosphate mixture was assessed by immersing the strip in water and subjecting it to ultrasonic cleaning for five minutes. The strips were dried in air and then examined by optical microscopy. Figures 2a and 2b show the results for bombarded and unbombarded regions on polypropylene and Mylar respectively.
The adherent membrane/calcium phosphate mixture appears darker in these micrographs. It is clearly seen that the membrane/calcium phosphate mixture is attached to bombarded regions and is removed from unbombarded virgin regions.
EXAMPLE 2
IgG was purified from human serum by
Sepharose-Staph A affinity column chromatography. An aliquot of the purified IgG was radiolabelled with 125I by the Chloramine T method. Radiolabelled IgG was added to the purified IgG as a tracer to give a ratio of labelled to unlabelled IgG of between 1:20 and 1:30.
This radiolabelled material was then used to examine the influence of IgG concentration, buffer pH and reaction time on the interaction of IgG with ion bombarded plastic surfaces.
In these experiments IgG was diluted in phosphate buffer pH 7.0 and carbonate buffer pH 9.6 over a concentration range of lOμg/ml to lOOμg/ml. 40μl samples were applied to wells (0.6cm diameter) impressed on ion bombarded and virgin plastic strips. Following incubation at room temperature the strips were rinsed with deionised water, the wells cut from the strip and the radioactivity due to adherent IgG counted in a γ counter.
It was found that buffer pH did not significantly influence the amount of IgG bound to the ion bombarded plastic surfaces. Longer reaction times (18 to 20 hours) permitted the attachment of more IgG. The higher concentrations of IgG resulted in more IgG attaching to the ion bombarded plastics.
Table 1 indicates the influence of different forms of ion bombardment and different plastics on the uptake of IgG. This clearly shows that ion bombardment can increase the uptake of IgG to plastic surfaces and that the efficiency varies depending on the species of the ion employed and the type of plastic used.
TABLE 1 Typical results on ion beam induced enhancement (in per cent) in attachment of IgG to various plastic substrates.
Bombarded Ion Species
Plastic Substrate Helium Argon
Polypropylene 288 349
Teflon 128 42
Polystyrene 113 89
It will be appreciated that the above Examples are given only by way of illustration of the present invention, and that many modifications and variations may be made thereto without departing from the scope of the invention as broadly described herein.
REFERENCES
1. Engvall, E. , Methods in Enzymology 1980; 7_0 : 419-439.
2. Chessum, B.S. & Denmark, J.R., Inconstant ELISA Lancet, 1978; i:161.
3. du Plessis, T.A. and Schnauz, N.G. - J.Oil Col. Chem.Assoc. , 1975; 58^, pp 85-89.
4. Heuser, C.H., Stocker, J.W., and Gisler, R.H. - Methods of binding cells to plastics: Application to solid phase immunoassays for cell-surface antigens. Methods in Enzymology, 1981; 7_3_, 406.
5. Dearnaley, G. , Freeman, J.H., Nelson, R.S. and Stephen, J. Ion Implantation (North Holland, Amsterdam, 1973) .
6. Bodδ, P. and Sundgren, J.-E. - Adhesion of evaporated titanium to polyethylene: Effects of ion bombardment pretreatment. J.Vac.Sci.Technol. A. Vol.2, No.4., Oct-Dec. 1984.
7. Frank, H.P., 'Polypropylene' (McDonald Tech., London, 1968) , Chapter 5.
8. Klarkowski, D.B. - A calcium phosphate co-sedimentation method for the preparation of haemoglobin free human erythrocyte stro a. Australian Journal of Medical Laboratory Science 1984, 5_ pp.124-126.

Claims

CLAIMS :
1. A method of attaching a biological substance to a solid-phase substrate which comprises the steps of (i) subjecting a solid-phase substrate to ion bombardment, and (ii) contacting the treated substrate with a biological substance to be attached thereto.
2. A method according to claim 1 wherein the said substrate is selected from the group of materials consisting of plastics, glass and silica, and cellulose and cellulose derivatives.
3. A method according to claim 2, wherein the said plastics material is selected from the group consisting of polypropylene, polystyrene. Teflon, Mylar and latex.
4. A method according to any one of claims 1 to 3, wherein the said biological substance is selected from the group consisting of immunoglobulins, allergens, cells and cellular material, enzymes and hormones.
5. A method according to claim 4, wherein the said biological substance is an immunoglobulin selected from the group consisting of IgG, IgM and IgE.
6. A method according to claim 4 , wherein the said biological substance comprises cells or cellular material selected from the group consisting of red blood cell membranes, leucocytes, platelets, bacteria and viruses.
7. A method according to claim 4, wherein the said biological substance is glucose oxidase.
8. A product produced by the method according to any one of claims 1 to 7.
9. A product comprising a solid-phase substrate, the surface of which has been treated by ion bombardment, and a biological substance attached to said treated surface.
PCT/AU1986/000235 1985-08-19 1986-08-18 Method of attaching biological substances to solid substrates WO1987001120A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
BR8606830A BR8606830A (en) 1985-08-19 1986-08-18 PROCESS FOR CONNECTING BIOLOGICAL SUBSTANCES TO SOLID SUBSTRATES
HU864075A HUT43092A (en) 1985-08-19 1986-08-18 Process for binding biological materials to solid vehicles
FI871599A FI871599A0 (en) 1985-08-19 1987-04-13 FOERFARANDE FOER ANSLUTNING AV BIOLOGISKA AEMNEN TILL FASTA SUBSTRAT.
DK200387A DK200387D0 (en) 1985-08-19 1987-04-15 PROCEDURE FOR ADJUSTING BIOLOGICAL SUBSTANCES TO SOLID SUBSTRATES

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AUPH202785 1985-08-19
AUPH2027 1985-08-19

Publications (1)

Publication Number Publication Date
WO1987001120A1 true WO1987001120A1 (en) 1987-02-26

Family

ID=3771228

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/AU1986/000235 WO1987001120A1 (en) 1985-08-19 1986-08-18 Method of attaching biological substances to solid substrates

Country Status (7)

Country Link
EP (1) EP0233257A4 (en)
JP (1) JPS63500893A (en)
BR (1) BR8606830A (en)
DK (1) DK200387D0 (en)
FI (1) FI871599A0 (en)
HU (1) HUT43092A (en)
WO (1) WO1987001120A1 (en)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989010377A1 (en) * 1988-04-20 1989-11-02 Washington Research Foundation Tight binding of proteins to surfaces
EP0502633A2 (en) * 1991-03-07 1992-09-09 Minnesota Mining And Manufacturing Company Surface modification by accelerated plasma or ions
WO1997012752A2 (en) * 1995-10-06 1997-04-10 Kaeufer Helmut Biocompatible plastics, process for producing the same and fields of use
TWI464403B (en) * 2008-03-31 2014-12-11 Asahi Kasei Fibers Corp Cellulose derivative fine particles, a dispersion thereof, a dispersion thereof and a diagnostic agent

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU553464B2 (en) * 1981-03-24 1986-07-17 Behringwerke Aktiengesellschaft Irradiated immunological carrier and preparation

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5980442A (en) * 1982-09-24 1984-05-09 ベクトン・デイツキンソン・アンド・カンパニ− Chemically modified surface for bonding large molecule

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU553464B2 (en) * 1981-03-24 1986-07-17 Behringwerke Aktiengesellschaft Irradiated immunological carrier and preparation

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, Volume 101, No. 24, issued 1984, December 10, (Columbus, Ohio, USA), Z.W. KOWALSKI "Investigation of the Surface Morphology of Ionbombarded Biocompatible Materials with a SEM and Profilograph, see page 362 column 2, Abstract No. 217039h, J. Mater. Sci 1984 19(4) 2845-54 *
S.R. TAYLOR, D.F. GIBBONS "Effect of Surface Texture on the soft Tissue Response to Polymer Implants "Journal of Biomedical Materials Research" Vol. 17, pp. 205-227 (1983) by JOHN WILEY & Sons, Inc. *
See also references of EP0233257A4 *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989010377A1 (en) * 1988-04-20 1989-11-02 Washington Research Foundation Tight binding of proteins to surfaces
EP0502633A2 (en) * 1991-03-07 1992-09-09 Minnesota Mining And Manufacturing Company Surface modification by accelerated plasma or ions
EP0502633A3 (en) * 1991-03-07 1993-04-07 Minnesota Mining And Manufacturing Company Surface modification by accelerated plasma or ions
US5389195A (en) * 1991-03-07 1995-02-14 Minnesota Mining And Manufacturing Company Surface modification by accelerated plasma or ions
WO1997012752A2 (en) * 1995-10-06 1997-04-10 Kaeufer Helmut Biocompatible plastics, process for producing the same and fields of use
WO1997012752A3 (en) * 1995-10-06 1997-06-05 Helmut Kaeufer Biocompatible plastics, process for producing the same and fields of use
TWI464403B (en) * 2008-03-31 2014-12-11 Asahi Kasei Fibers Corp Cellulose derivative fine particles, a dispersion thereof, a dispersion thereof and a diagnostic agent
US9096690B2 (en) 2008-03-31 2015-08-04 Asahi Kasei Fibers Corporation Cellulose derivative fine particle, dispersion liquid thereof, dispersion body thereof and diagnostic reagent
US9341622B2 (en) 2008-03-31 2016-05-17 Asahi Kasei Fibers Corporation Cellulose derivative fine particle, dispersion liquid thereof, dispersion body thereof and diagnostic reagent

Also Published As

Publication number Publication date
DK200387A (en) 1987-04-15
EP0233257A1 (en) 1987-08-26
FI871599A (en) 1987-04-13
DK200387D0 (en) 1987-04-15
BR8606830A (en) 1987-10-27
FI871599A0 (en) 1987-04-13
JPS63500893A (en) 1988-03-31
EP0233257A4 (en) 1989-01-26
HUT43092A (en) 1987-09-28

Similar Documents

Publication Publication Date Title
CA1303981C (en) Polymer-coated optical structures
US4357311A (en) Substrate for immunoassay and means of preparing same
US3966897A (en) Medium for use in bioassay and method of using same
US3790663A (en) Preparation of dry antiserum coated solid-phase for radioimmunoassay of antigens
US3926564A (en) Substrate for immunological tests and method of fabrication thereof
US4041146A (en) Method for detection of biological particles
US4090850A (en) Apparatus for use in radioimmunoassays
US4092116A (en) Method for binding antibodies to a surface such that they remain active
US3960491A (en) Method and apparatus for detecting immunologically reactive biological particles
US4410660A (en) Binding assay for the detection of mycobacteria
JPS5980442A (en) Chemically modified surface for bonding large molecule
US4575484A (en) Binding assay for the detection of mycobacteria
JPH0543600A (en) Antibody-or antigen-immobilized silk fibroin membrane and sensor for measuring immune
WO1987001120A1 (en) Method of attaching biological substances to solid substrates
US4489158A (en) Binding assay for the detection of mycobacteria
AU605746B2 (en) Method of attaching biological substances to solid substrates
Ekdahl et al. Complement activation on radio frequency plasma modified polystyrene surfaces
Ghourchian et al. Latex piezoelectric immunoassay: effect of interfacial properties
CA1187786A (en) Agent for immunological diagnosis and a process for its preparation
JPS60222774A (en) Activated solid phase body and activating method thereof andimmunological reactive solid phase body and manufacture and check method thereof
WO1995034814A1 (en) Plasma treatment of polymeric materials to enhance immobilization of analytes thereto
Hunter et al. Interactions of Neutral Amino Acids with Human Serum Albumin and γ-Globulin1
JPH01305100A (en) Stabilization of immobilized biologically active substance
Kumakura et al. Immobilization of antibodies and enzyme-labeled antibodies by radiation polymerization
Kurosawa et al. Adsorption of F (AB') 2 Anti-Human Immunoglobulin G to Plasma-Polymerized Allylamine Film Covered on a Silver Plate

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AU BR DK FI HU JP US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE FR GB IT LU NL SE

WWE Wipo information: entry into national phase

Ref document number: 871599

Country of ref document: FI

WWE Wipo information: entry into national phase

Ref document number: 1986905147

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1986905147

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 1986905147

Country of ref document: EP