Scientific publications and patent applications of L.P.C. Kuijpers

Scientific publications and patent applications of
L.P.C. Kuijpers
(also spelled L.P.C. Kuypers)
(and some graduation reports of laboratory research trainees under his responsibility)

This survey concerns my published scientific contributions to the development and subsequent improvements of the first commercial micro-Elisa, a very successful diagnostic laboratory test system. Starting with hepatitis B, Elisa-technology it is now used worldwide for routine screening and follow-up of many infectious diseases. This includes testing for infectious markers in transfusion blood and blood products and follow-up testing in anti-viral therapies including vaccination programs.

Based on comprehensive expertise with micro-Elisa technology, Organon Teknika in Boxtel, The Netherlands, was also able to develop at top-speed the first commercial screening test for anti-HIV (marker for HIV-infection that may lead to AIDS). The early availability of this important diagnostic tool saved numerous lives worldwide, like was already the case with micro-Elisa for hepatitis B and other infectious diseases.

This survey is also to honour my colleagues for the offered opportunities, their excellent scientific support and guidance during my episodes at the Scientific Research & Development Laboratories of Organon International (interim Schering-Plough; today MSD) in Oss , The Netherlands and the Diagnostics Research Laboratories of Organon Teknika (today Biomerieux) in Boxtel, The Netherlands and in Durham, North Carolina, USA.

Leo Kuijpers, biochemical researcher
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Scientific publications
("J. Kacaki" should be written with a small v on top of the letter c and is also spelled "J. Katchaki")

1976. Wolters, G., L. Kuijpers, J. Kacaki and A. Schuurs.
Solid-phase enzyme-immunoassay for detection of hepatitis B surface antigen.
J. Clin. Pathol. 29, 873-879 (1976).
Preliminary results of a solid-phase enzyme-immunoassay (EIA) for the detection of hepatits B surface antigen are presented. The test has been compared with the solid-phase radioimmunoassay for this antigen by four national reference panels.

1976. Wolters, G., L. P. C. Kuijpers, J. Kacaki and A. H. W. M. Schuurs.
Enzyme-immunoassay for HBsAg.
Lancet 690 (1976).
In a letter to the editor the authors remark that they have developed an enzyme-immunoassay for HBsAg and that the results of a multicentre trial of this test will be published elsewhere.

1976. Wolters, G., L. P. C. Kuijpers, A. H. W. M. Schuurs, and J. Kacaki.
Enzyme-immunoassay (EIA) of hepatitis B surface antigen (HBsAg) in microtiter plates.
Z. Anal. Chem. 279, 144 (1976).
For the development of the above-mentioned assay the authors used the sandwich technique with a solid-phase antibody and an enzyme-labelled antibody. Methods and results are described.

1976. Festphasen Enzym-Immunoassay zum nachweis von Hepatitis B-surface Antigen.
G. wolters, L. Kuijpers, J. Kacaki und A.H.W. Schuurs.
Organon Teknika. Medizinische Produkte GmbH. REFERAT 1976?
Enzym-Immunoassay (EIA) und Radio-immunoassay (RIA) wurden in einer wöchentlichen Untersuchung von 14 Patienten mit akuter Virushepatitis B (bis zu 16 Wochen rang) verglichen. Die Sensitivität und Spezifität der EIA-Methode, sowohl durch Ablesen mit bloßem Auge als auch durch kolorimetrische Bestimmung, lassen sich sehr gut vergleichen mit derjenigen des RIA's.

1977. Wolters, G., L.P.C. Kuijpers, J. Kacaki, and A.H.W.M. Schuurs.
Enzyme-linked immunosorbent assay for hepatitis B surface antigen.
J. Infect. Dis. 136, S311-S317 (1977).
The results obtained from a multicentre study using a solid-phase enzyme- linked immunosorbent assay based on the "sandwich" principle for the detection of hepatitis B surface antigen in blood of donors and in blood of patients with hepatitis B are reported.

1977. Kacaki, J., G. Wolters, L.Kuijpers and A. Schuurs.
Specificity control in solid phase enzyme immunoassay for HbsAg by one-step in situ blocking with human anti-HBs.
J. Clin. Pathol. 30, 894-898 (1977)
Two confirmatory methods of solid-phase enzyme-immunoassay for HBsAg were compared. The "blocking method", where one-step insitu blocking with human anti-HBs was applied, was found superior to the "dilution method".

1977. Waart, M.v.d., A. Bosch, G. Wolters, L.Kuijpers, B. van Weemen and A. Schuurs.
Enzyme-immunoassay; a new diagnostic tool.
Chem. Rundsch. 30 No 28, 1-2 (1977).
This survey deals with some general principles of enzyme-immunoassay (EIA), with some specific examples and with some characteristics of EIA, in particular the attainable sensitivity. A comparison between EIA, radioimmunoassay and immunofluorescence is given.

1977. Weemen, B. van, A. Bosch, J. Brands, H. van Hell, L. Kuijpers, A. Schuurs and G. Wolters.
Enzyme-immunoassay for HbsAg, HPL and estrogens in serum.
Clin. Biochem. 10. No 2, P6-P7 (1977).
This is a short account of the development on enzyme-immunoassays for HBsAg, human placental lactogen and estrogens in serum, using the enzyme horse-radish peroxidase as a label for either antibody or antigen.

1977. Weemen, B.K. van, A.M.G. Bosch, H. van Hell, J.A.M. Brands, G. Wolters. L.P.C. Kuijpers and A.H.W.M. Schuurs.
Enzyme immunoassay.
In: Siest, G. ed.. Troisième coloque international organisé par l'Association Recherche Biochemique et Pharmaceutique, Lorraine, 1975 (Fr).
Paris, Expansion Sci. Fr., (1977). pp 615-621.
The significance and the technique of enzyme-immunoassay (EIA) are described. It is concluded that EIA, in its various modifications, offers an opportunity to the general, unspecialized laboratory to apply highly sensitive and specific assay techniques, without the need to acquire new and expensive equipment and technology.

1977. Wolters, G., L. Kuijpers, J. Kacaki and A. Schuurs.
Enzym-Immunaassay zum Nachweis von HBsAg.
In: Matthes, M., und V. Nagel (Hrsg.)
Forschungsergebnisse der Transfusionsmedizin und Immun-haematologie; Band 3; Bericht des 17. Kongresses der Deutschen Gesellschaft für Bluttransfusion und Immun-haematologie vom 26. bis 29. April 1976 in Frankfurt.
Berlin, Medicus Verl., (1977). p. 63-67.
A new enzyme-immunoassay (EIA) for hepatitis B-surface antigen (HBsAg) is described. It is concluded that EIA is a simple and modern method for the laboratory to test blood donors and patients.

1977. Wolters, G., L. P. C. Kuijpers, J. Kacaki and A. H. W. M. Schuurs.
Enzyme-immunoassay for hepatitis B surface antigen.
Abstr. of paper presented at 22e Convegno di studi della Societa Italiana di Immunoematologia e Associazione Italiana del Centri Transfusionali; 14-18 Settembre, 1977. Abstr. No.26.
The technique of a solid-phase enzyme-immunoassay for the detection of hepatitis B surface antigen in human serum or plasma is briefly described. The test appeared to have a similar sensitivity to that of radioimmunoassay and to yield more favourable results than the reversed haemagglutination test.

1977. Wolters, G., L. Kuijpers and A. Schuurs.
Enzyme-immunoassay as a diagnostic tool in viral hepatitis B.
Abstr. of poster presented at Meeting European Group for Rapid Laboratory Viral Diagnosis and 16th Symposium European Association Against Virus Diseases; Amsterdam, 6-9 Sept. 1977.1 p.
The development of an enzyme-immunoassay (EIA) for the detection of hepatitis B surface antigen and the development of an EIA-inhibition method for the detection of antibody against this antigen are briefly described.

1978. Kacaki, J., G. Wolters, L.Kuijpers and S. Stulemeyer.
Results of a multicentre clinical trial of the solid-phase enzyme immunoassay for hepatitis B surface antigen.
Vox Sang. 35, 65-74 (1978)
The results of this multicentre clinical trial showed that the enzyme- immunoassay for hepatitis B surface antigen has a significantly higher sensitivity than the reversed haemagglutination test and that there was an excellent agreement between the new method and radio-immunoassay.

1978. Wolters, G., L. P. C. Kuijpers, J. Kacaki and A. H. W. M. Schuurs. Enzyme-immunoassay for hepatitis B surface antigen.
In: B. K. van Weemen (ed.)
Enzyme-immunoassay; Proc. of a symp. held in the Dr. Saal van Zwanenberg Auditorium, Oss, September 24, 1976. Oss, Organon (1978). p. 77-88.
The results obtained with a new enzyme-immunoassay (EIA) for hepatitis B surface antigen (HBsAg) are described. It is concluded that EIA represents an easy and modern answer to the required highly sensitive HBsAg detection in blood from donors and patients which is also suitable for less well-equipped laboratories.

1979. Results of a Multicentre Clinical Trial of the Solid-Phase Enzyme Immunoassay for Hepatitis B Surface Antigen
J. Kacaki, G. Wolters, L. Kuijpers and S. Stulemeyer
In: Jovan Kacaki at University of Nijmegen, thesis, April 6 1979, p20-29.
The results obtained in a multicentre clinical trial of an enzyme immunoassay (Elisa) method for hepatitis B surface antigen (HBsAg) (65451 sera tested) demonstrated that this new test has a significantly higher sensitivity than a reversed haemagglutination test (rHA). In a part of the trial, Elisa was also compared with radioimmunoassay (RIA). Only a small number of discrepant results was obtained with these two tests, indicating similar sensitivities. Presumptive positives in Elisa were subjected to a confirmatory test based on neutralization with human antibodies to HBsAg. After elimination of false positives in Elisa and RIA there was an excellent agreement between the two testsystems.

1979. Wolters, G., L. Kuijpers and A. Schuurs.
Detection of human antibodies to hepatitis B surface antigen (HBsAg) by an enzyme-immunoassay for HBsAg.
J.Clin.Pathol. B, 1264-1271 (1979).
The feasibility of detecting antibody to hepatitis B surface antigen by an inhibition assay using the reagents of an enzyme-immunoassay for HBsAg (Hepanostika) was studied. The applied modifications, the advantages of the method and results are discussed.

1980. Wolters, G. and L.P.C. Kuijpers.
Results obtained with Hepanostika: and enzyme-immunoassay for HBsAg.
Abstract of paper presented at the joint meeting of the 18th congress of the International Society of Hematology and 16th congress of the International Society of Blood Transfusion; Montreal, August 16-22, 1980. p.266 (Abstr.No.1436).
This is a short summary of the results of studies into the stability, total test duration, sensitivity and some other characteristics of Hepanostika.

1980. Wolters, G., L.P.C. Kuijpers and J. Croese.
Improved Hepanostika; an enzyme-immunoassay for hepatitis B surface antigen.
J.Virol.Methods 2, 57-62 (1980).
Test conditions and composition of some components of Hepanostika were modified in order to improve this enzyme-immunoassay with regard to test duration, sensitivity and reading of test results.

1981. Kuijpers, L., G. Wolters and A. Schuurs.
Large scale purification of hepatitis B surface antigen (HBsAg) by means of batchwise immune absorption.
In: International, 4th, symposium on affinity chromatography and related techniques i theoretical aspects, industrial and biomedical applications (Veldhoven, The Netherlands), June 22-26, 1981, abstracts.
A procedure for large-scale purification of hepatitis B surface antigen by means of batchwise immune absorption and two different methods for further purification are briefly described.

1982 .L. Kuijpers, H. Haas, G. Hotz, G. Wolters, A. Jacobs.
Incubation time and temperature influences on Microelisa Hepanostika HBsAg
Proceedings International Hepatitis Workshop, available from Nudear Enterprises Limited; Edinburgh, Scotland. 1982? SHORT COMMUNICATION
Hepanostika was evaluated with sera and plasma's, with incubation times varying from 0,5 upto 24 hours and with incubation temperatures varying between 20 and 50 ºC. It is concluded that Hepanostika HBsAg is a flexible test with regard to incubation times and temperatures. Preheating of plasma's for 0,5 hour at 56 ºC is indicated when using higher incubation temperatures.

1983. Heijtink, R. , J .Kruining , L.Kuijpers, A .Jacobs, C .Geudens and G.Wolters.
An ELISA for delta markers in hepatitis B infection.
In: Verme, G., F.Bonino and M.Rizzetto (eds.) Viral hepatitis and delta infection; Proceedings of an international symposium on viral hepatitis; Torino, June 10-11, 1983.
New York, Liss, 1983. p.263. Progress in Clinical and Biological Research, Vol.143.
The test principles and performance requirements of an ELISA for delta markers in hepatitis B infection as well as its specificity and high sensitivity are presented. It is concluded that this assay allows the detection of delta-antigen or delta-antibody in serum by the same test.

1983. Kuypers, L., R.A.Heytink, A.Jacobs, G.Wolters and J.Kruining.
Vaccination against hepatitis B: prescreening and follow-up by an ELISA detecting both HBsAg and anti-HBs.
Antonie van Leeuwenhoek 49, 601 (1983).
The results obtained with the use of ELISA for the detection of anti-HBs and HBsAg in serum indicate that this immunoassay is suitable for the prescreening and follow-up of vaccinees.

1983. Kuijpers, L., H. Haas, G.Hotz, G.Wolters and A.Jacobs.
Incubation time and temperature influences on microelisa Hepanostika HBsAg.
In: Hopkins, R., and S. Field (eds.)
Viral hepatitis; 2nd international workshop; Stirling (Scotland) ,
1-3 September. 1982. S.I., s.n., (1983). p.121-122.
Hepanostika HBsAg was investigated at varying incubation times and temperatures with blood donor sera, fresh patient sera and dilution series of HBsAg in serum. It is concluded that this test is a flexible one with regard to incubation times and temperatures ensuring a detection limit which is independent of the incubation procedure.

1983. Kuijpers, L., R.Heijtink, A.Jacobs and G.Wolters.
Vaccination against hepatitis B: prescreening and follow-up by an ELISA detecting both HBsAg and anti-HBs.
Neth.J.Med. 26., 206 (1983).
A single test, which detects HBsAg as well as anti-HBs, using a modified sandwich ELISA is described. As compared to RIA's for various HBV markers, this single test appeared pre-eminently suitable for the prescreening and follow-up of vaccinees.

1984. Kuijpers, L., R.A. Heytink, A. Jacobs and G. Wolters
Vaccinatie tegen hepatitis B: selectie en controle met een ELISA die zowel HBsAg als anti-HBs aantoont .
Ned.Tijdschr.Geneeskund. 128, 1029 (1984)
The authors tested 542 persons with an increased risk of hepatitis B with ELISA and with RIA's for HBsAg, anti-HBs and anti-HBc. The results showed that ELISA is a very suitable test for the selection and control of patients with an increased risk for hepatitis B before vaccination against this virus.

1984. Kuijpers, L.P.C., R.A. Heytink, A.J.J.M. Jacobs, G. Wolters and J .Kruining.
Vaccinatie tegen hepatitis B: selectie en controle met een ELISA die zowel HBsAg als anti-HBs aantoont .
Ned.Tijdschr.Geneeskd. 128, 639-640 (1984) .
RIA and a sandwich ELISA were compared as methods for the investigation of HBsAg and anti-HBs in 542 patients who needed vaccination against hepati tis B. It is concluded that ELISA offers more advantages and
better results than RIA .

1984. Kuijpers, L., R. Heijtink, A. Jacobs, G. Wolters, and J. Kruining
An ELISA for the prescreening and follow-up in hepatitis B vaccination programmes.
In: International Society of Blood Transfusion. Abstracts of the 18th congress of the International Society of Blood Transfusion; Munich , 22-27 July, 1984.
Basel, Karger, 1984. p.117 (Ahstr.No.Pl-06) .
The procedure, results and advantages of an ELISA for the prescreening and follow-up in hepatitis B vaccination programmes in humans are briefly presented .

1984. Kuijpers, L., R. Heijting, A. Jacobs, G. Wolters, J. Kruining
An Elisa for the prescreening and follow-up in hepatitis B vaccination programmes.
In: International symposium, The 1984, on viral hepatitis; a contemporary assessment of the biology of viral agents, laboratory diagnosis, epidemiology , pathogenesis, prophylaxis ,
and clinical management of liver disease; San Francisco, March 8-10, 1984.
S.l., S.a., 1984. Abstr.No.8B.47.
The authors report a prevaccination screening study of more than 500 individuals with a risk of contracting hepatitis B and a follow-up study of more than l00 vaccinees showed that a sandwich ELISA could be used instead of RIA's for HBsAg and anti-HBs with good results.

1985. Wolters, G., P. Nelissen and L. Kuijpers
Improved ELISA for the detection of HBsAg.
J.Virol.Methods 10, 299-305 (1985)
The results of this study showed that by modifying some of the components of a previously developed ELISA for HBsAg, a new ELISA is feasible with improved sensitivity, specificity, practicability and speed.

1987. L. Kuijpers, M. Koens, A. Jacobs, P. Boon, and L. Matthijssen.
Pre-S1 and Pre-S2 Specific HbsAg and anti-HBs Sandwich Micro-Elisas Developed With Peptides.
In Arie J. Zuckerman (ed.) 1987 international symposium on viral hepatitis and liver disease. The sixth triannual meeting. Abstr. 198, page 69A.
Monoclonal antibodies (MCA), evoked in mice through immunization with an HbsAg/HbeAg serum pool, were selected on their reactivity with Pre-S1 12-32 and Pre-S2 119-145 synthetic peptides and non-reactivity with HbsAg in which the pre-S epitopes were destroyed by pepsine digestion. The peptides were also used to evoke anti-pre-S antibodies in sheep. The selected MCA's and sheep-antibodies were successfully applied to prepare pre-S and anti-pre-S specific micro-Elisa's.

1988. L. Kuijpers, M. Koens, A. Jacobs, P. Boon, and L. Matthyssen.
Pre-Sl- and Pre-S2-Specific HBsAg and Anti-HBs Sandwich Micro-ELISAs Developed With Synthetic Peptides
Viral Hepatitis and Liver Disease, pages 280-283 @ 1988 Alan R. Liss, Inc. (Editor A.J. Zuckerman)
Two synthetic peptides, representing parts of the preS region of HbsAg (preS1 12-32 and preS2 126-145) and antibodies against those peptides were used to compose anti-preS1, anti-preS2, preS1 and preS2, direct sandwich micro-Elisa's. The preS1 test was reactive with 140/171 sera with a high level of HBsAg, the preS2 test with all of 44 of such sera. In the anti-preS1 and anti-preS2 test 0 and 11 out of 105 human anti-HBs sera were reactive.

1989. Leo Kuijpers, Marjolijn Koens, John Murray-Lyon, Jon C. Coleman, Peter Karayiannis,
Pre-S Proteins in Hepatitis B
Howard C. Thomas, Alessandro Zanetti, A. Cargnel, Tim J. Harrison, and Arie J. Zuckerman
Scientific Development Group, Organon International BV, Oss, Netherlands (L.K., M.K.); Charing Cross Hospital (l.M.-L., J.C.C., A.J.Z.), St Mary's Hospital Medical School (P.K., H.C.T.), and London School of Hygiene and Tropical Medicine (T.J.H., A.J.Z.), London, England; Institute of Virology (A.Z.), and Hospital L Sacco (A.C.), Milan, Italy.
Journal of Medical Virology 28:47-51 (1989)
Using pre-S specific micro-Elisa it was shown that pre-Sl reactivity was closely related to the presence of HBV-DNA, whereas pre-S2 proteins correlate far less well with viral replication as shown by the presence of pre-S2 in sera in which HBV-DNA is no longer detectable. Loss of HBV-DNA and of HBeAg followed by seroconversion to anti-HBe in patients after treatment with interferon was associated with loss of pre-Sl proteins. Failure to respond to treatment did not result in a significant loss of pre-Sl and pre-S2 proteins.

1990. T.J.M. van Ditzhuijsen, L.P.C. Kuijpers, M.J. Koens. P.J.M. Rijntjes. A.M. van Loon, and S.H. Yap
Hepatitis B Pre-Sl and Pre-S2 Proteins: Clinical Significance and Relation to Hepatitis B Virus DNA
Division of Gastrointestinal and Liver Diseases, Departments of Medicine (T.J.M. v D.) and of Medical Microbiology (A.M.v.L.), St Radboud University Hospital, Nijmegen and Diognostics Research Laborolories, Organon, Oss (L.P.C.K., M.J.K. P.J.M.R.), The Netherlands; Division of Liver and Pancreatic Diseases, University Hospital Gasthuisberg, Leuven, Belgium (S.H.Y.)
Journal of Medical Virology. Accepted for publication June 29, 1990
Pre-S1 and pre-S2 proteins were detected in nearly all HbsAg/HbeAg positive patients. HBV-DNA was found in approx 70% of these sera. In HBsAg/anti-HBe patients also pre-S1 and pre-S2 proteins were detected despite the absence of HBV-DNA. However sera of HBsAg positive patients that were negative for both anti-HBe and HBeAg only a minority was reactive for pre-S proteins.

Patent applications

19820817. Improved visual reading of colour tests
Publication number: EP0103915, B1
Publication date: 1984-03-28
Inventor: GRIBNAU THOMAS CORNELIS JOSEPH; KUYPERS LEONARDUS PAULUS CLEMENS
Applicant:: AKZO NV (NL)
Publication: DE3374877D
Application number: EP19830201089 19830725
Priority number: NL19820003221 19820817
IPC Classification: C12Q1/00 ; G01N31/22 ; G01J3/46
EOB Classification: G01N33/52, G01N33/53, G01N31/22
Equivalents: NL8203221
Abstract: A new method for the visual detection of the colour of a liquid in a series of vessels containing different dyestuff concentrations is described, in which the detection is carried out in the presence of one or more additional dyestuffs, resulting in the observation of different colours or colour shades in the vessels containing different concentrations of the first dyestuff.

19830608. Determination of delta-antigens in body fluids.
Publication number: EP0131974
Publication date: 1985-01-23
Inventor: KUYPERS LEONARDUS PAULUS CLEMENS; WOLTERS GERRIT
Applicant:: AKZO NV (NL)
Publication: DK283484
Application number: EP19840200762 19840525
Priority number: NL19830002038 19830608
IPC Classification: G01N33/53
EOB Classification: G01N33/576D
Equivalents: FI842276, JP60024451
Abstract: The present invention concerns a method for detection of the HBV associated S-antigen in a sample comprising a first incubation with carrier-bonded anti-HBs and a second incubation with anti- delta in the presence of a detergent. Also claimed are test kits for carrying out this method and an immunochemical reagent comprising anti-HBs and anti-delta conjointly bonded to a carrier.

19830914. Method for the immunochemical determination of hepatitis B core antigens
Publication number: US4701410
Publication date: 1987-10-20
Inventor: KUYPERS LEONARDUS P C (NL); WOLTERS GERRIT (NL)
Applicant:: AKZO NV (NL)
Publication: US4701410
Application number: US19840645064 19840828
Priority number: NL19830003169 19830914
IPC Classification:
EOB Classification: G01N33/576B2
Equivalents: CA1229790, DE3477610D, DK159297B, DK159297C, DK439684, EP0139316, FI78181B, FI78181C, FI843562, JP1862212C, JP5076582B, JP60095356
Abstract: The present invention concerns a method for detection of the core antigen of hepatitis B virus in a sample comprising a first incubation with carrier-bound antibodies directed against hepatitis B surface antigens and a second incubation with antibodies against the core antigen in the presence of a detergent. Also claimed are test kits for carrying out this method and an immunochemical reagent comprising antibodies directed against the surface antigen and against the core antigen conjointly bound to a carrier.

19840827. Determination of protecting anti-HBV immunoglobulins
Publication number: US4701421
Publication date: 1987-10-20
Inventor: KUYPERS LEONARDUS P C (NL); MATTHYSSEN LUDOVICUS F T (NL)
Applicant:: AKZO NV (NL)
Publication: US4701421
Application number: US19840644440 19840827
Priority number: US19840644440 19840827
IPC Classification:
EOB Classification: G01N33/543B, G01N33/576B4
Equivalents:
Abstract: A novel method for the determination of protecting anti-HBV immunoglobulins is based on the use of two different HBsAg reagents: one insolubilized and having the antigenic type AX and one labelled and having the antigenic type AY, wherein A represents the epitope or epitopes which are common to all HBsAg serotyes, wherein X and Y both represent combinations of the epitopes which are not common to all HBsAg serotypes, and where the combinations X and Y have no epitopes in common.

19850819. Device for the carrying out of an immunochemical determination
Publication number: US4780285
Publication date: 1988-10-25
Inventor: KUYPERS LEONARDUS P C (NL); WOLTERS GERRIT (NL)
Applicant:: AKZO NV (NL)
Publication: US4780285
Application number: US19860893511 19860805
Priority number: NL19850002271 19850819
IPC Classification:
EOB Classification: G01N33/543K
Equivalents: AU591921, AU6108286, CA1272950, DE3666982D, DK163021B, DK163021C, DK392286, EP0213653, B1, ES2000145, FI84301B, FI84301C, FI863319, GR862039, HU46146, IE59050, JP1939358C, JP6065988B, JP62071859, KR9601827, NO168274B, NO168274C, NO863318, PT83194, RU2080599, ZA8605753
Abstract: Device for the carrying out of an immunochemical determination comprising at least one holder which is provided with an opening at the top and to the inside of which an immunochemically active substance has been applied. The device is closed at the top by a removable closure means and the holder contains at least a second immunochemically active substance which, in the absence of test medium, in the form in which the second immunochemically active substance is contained in the closed holder, during storage and transport under normal conditions exhibits no interaction with the inside of the holder and is inert with respect to the immunochemically active substance applied thereto. The holder contains a solid, more or less spherical, freeze-dried particle which contains the second immunochemically active substance.

19880406. Method for suppressing partial coloration in immunoassays utilizing peroxidase labels
Publication number: US5294535
Publication date: 1994-03-15
Inventor: GOOSSENS PETRUS ADRIANUS LEONA (NL); GRIBNAU THOMAS CORNELIS JOSEPH (NL); KUIJPERS LEONARDUS PAULUS CLEM (NL)
Applicant:: AKZO NV (NL)
Publication: US5294535
Application number: US19920944760 19920914
Priority number: US19920944760 19920914; NL19880000874 19880406; US19890334020 19890405; US19900627570 19901211
IPC Classification: C12N9/96 ; C12Q1/28 ; G01N33/535
EOB Classification: G01N33/535, G01N33/58B
Equivalents:
Abstract: The invention concerns a method for detecting an analyte in a blood sample or a derived fraction thereof. In this method one uses the binding affinity between the analyte and its specific binding agent. Moreover, a reaction component containing a peroxidase label is added to the sample and specific binding agent to form a reaction mixture. The incubation of the reaction mixture, containing the analyte and its specific binding agent, with the peroxidase-labeled reaction component has to be carried out in the presence of a quaternary ammonium salt or ionic surfactant.

19890615. Method for determining nucleic acid.
Publication number: EP0402997, A3, B1
Publication date: 1990-12-19
Inventor: RIJNTJES PETRUS JOHANNES MARIA (NL); KUIJPERS LEONARDUS PAULUS CLEM (NL); HEIJTINK RUDOLF ARNOLD (NL)
Applicant:: AKZO NV (NL)
Publication: AU641399
Application number: EP19900201480 19900608
Priority number: NL19890001512 19890615
IPC Classification: C12Q1/68 ; C12Q1/70 ; G01N33/569 ; G01N33/576
EOB Classification: C12Q1/70B6, G01N33/576B, C12Q1/68A2, C12Q1/70B2B
Equivalents: AU5716090, CA2018877, DE69012440D, DE69012440T, ES2063902T, IE64040, JP3033656, ZA9004600
Abstract: The invention relates to a method for the qualitative and/or quantitative determination of nucleic acid in a test fluid by binding biological particles present in the test fluid to a solid carrier by means of an immunochemical reaction. Thereafter the bound biological particles are lysed and the liberated nucleic acid is amplified. A test kit for carrying out the determination is also part of the invention.

19901008. Device for performing a rapid single manual assay.
Publication number: EP0480497
Publication date: 1992-04-15
Inventor: UYLEN MARCELUS HENDRIKUS FRANC (NL); KUIJPERS LEONARDUS PAULUS CLEM (NL)
Applicant:: AKZO NV (NL)
Publication: EP0480497, B1
Application number: EP19910202482 19910925
Priority number: EP19910202482 19910925; EP19900202666 19901008
IPC Classification: G01N33/543 ; G01N33/558 ; G01N33/576
EOB Classification: G01N33/543K, G01N33/558
Equivalents:
Abstract: Device for performing an assay in order to detect and/or determine an analyte in a test liquid, said device comprising a track for liquid transport, at least partly bordered by a semi-permeable layer, in said track during the assay and alongside the semi-permeable layer is transported a movable solid phase material bearing a ligand capable to bind, directly or indirectly, the analyte and/or to bind, directly or indirectly, a reactant for the analyte, said semi-permeable layer being incapable to let pass the movable solid phase material.

19901008. Semi-permeable capillary assay device
Publication number: US5474902
Publication date: 1995-12-12
Inventor: UYLEN MARCELUS H F (DE); KUIJPERS LEONARDUS P C (DE)
Applicant:: AKZO NOBEL NV (NL)
Publication: US5474902
Application number: US19940190699 19940202
Priority number: US19940190699 19940202; EP19900202666 19901008; US19910772768 19911007
IPC Classification: G01N33/543 ; G01N33/546 ; G01N33/553
EOB Classification: G01N33/543K, G01N33/558
Equivalents:
Abstract: A method and a device for performing an assay in order to detect or determine the amount of an analyte in a test liquid, wherein bound and unbound reactants can be separated, comprising a capillary canal for liquid transport that is at least partly bordered by a semi-permeable layer, wherein during performance of an assay a movable solid phase material bearing a ligand capable of binding the analyte or binding a reactant for the analyte is within the capillary channel adjacent to the semi-permeable layer, said semi-permeable layer having pores that are sufficiently small to prevent the passage of the movable solid phase material and sufficiently large to permit passage of unbound reactants there through.

19921103?. "New Enzymatic detection system".
William Bains and Leo Kuijpers.
? 1992-11-03 ?
UK Patent application number 9223018.4 (3/11/1992) (90.202.665.5).
Abstract: Not available

Graduation reports of students
trained under responsibilty of Leo Kuijpers, amongst others.

To obtain a batchelor or equivalent degree in (bio)chemical technology

1981. Basic investigations towards improved hepatitis tests: coupling immuneglobulines onto erythrocytes and application of monoclonal antibodies (in Dutch)
Joke Ederveen, Oss, February 1981

1981. Immunological reactivity of the hepatitis B surface antigen in relation to human serum albumin and antibodies against the latter. (in Dutch)
Joke Ederveen, Oss, May 1981

1984. Development of a direct sandwich Elisa for anti-HBs (in Dutch)
André Riswick, Oss, March 1984

1986. Design and evaluation of at least one pre-S specific HbsAg and/or anti-HBs test (in Dutch)
Rinie van Beuningen, Oss May 1986

1987. Hepatitis B test exploration with pre-S1 specific reagents. (in Dutch)
Ingeborg Struijk, Oss, January 1987

1988. Research towards practical possibilities for a rapid and simple test based on the determination of surface antigens. (in Dutch)
Dré Oomen, Oss, June 1987

To obtain a master degree at the University of Nijmegen, The Netherlands.

1989. Development of a Dane particle specific HBV assay. DNA amplification after Dane particle capture onto solid phase sheep anti-pre-S1 immunoglobulin.
Bernhard Kleter 1989.

Added keywords: agent analysis analyst analyte analytical methods antibody anti-HIV Australia antigen biochemical biochemist blood bank blood donor blood transfusion Blumberg boxtel02 chemist clinical lab colorimetric reading contagious curriculum vitae detection limit diagnosis diagnostica diagnostics discoveries discovery elimination employee Europe germ health healthy hepatitis A hepatitis C hepatitis D hepatitis E history HIV illness isolation invention jaundice laboratory techniques Leo Kuijpers Halderheiweg 24 Boxtel Leo Kuipers Leo Kuypers literature merits observation optimization papers presentations prevention probe proceedings production profession researcher science scientist screening testing