Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Reexamination Certificate
1999-03-23
2003-09-30
Marschel, Ardin H. (Department: 1631)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
C422S050000, C422S051000, C422S051000, C422S068100, C422S069000, C422S129000, C436S501000, C536S022100, C536S024300, C536S025300
Reexamination Certificate
active
06627397
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a surface plasmon resonance biosensor, specifically, a measuring chip for the same and a method for producing the measurement chip.
2. Background Art
A number of methods using immunological reactions are used in clinical tests for detecting target substances. Conventional methods are known to be intricate and require labeling substances. Thus, immunological sensors using a surface plasmon resonance biosensor (SPR) is being used, in which no labeling substance is required and a ligand can be detected with high sensitivity. This surface plasmon resonance biosensor is based on the phenomenon that the intensity of a monochromatic light reflected from the interface between an optically transparent substance such as glass and a metal thin-film layer is dependent on the refractive index of a sample placed on the reflecting side of the metal. Accordingly, a sample can be analyzed by measuring the intensity of the reflected monochromatic light.
An optical part of a measuring cell for this surface plasmon resonance (surface plasmon resonance biosensor) has a structure shown in FIG.
2
. Namely, porous material
5
is formed on metal thin-film
2
formed on glass substrate
1
, and physiologically active substance
4
, such as an enzyme or antibody, is retained or immobilized on the surface or inside of porous material
5
. Examples of porous material
5
to be used include weaved, knitted or non-woven cloths made of synthetic fibers, natural fibers, inorganic fibers or the like, and porous inorganic or organic materials (see Japanese Patent Laid-open No. 164195/1991). Furthermore, carboxymethyl dextran is used as a porous material in a commercial product (BIAcore 2000, Pharmacia Biosensor).
However, physiologically active substance
4
just exists on the surface of porous material
5
and interacts with target substances.
LB (Langmuir-Blodgett) method is occasionally used to immobilize physiologically active substance
4
on metal thin-film
2
(see Japanese Patent Laid-open No. 288672/1993). However, this method has a disadvantage in that LB membrane binds poorly to a metal thin-film and peels off together with the physiologically active substance.
Furthermore, Japanese Patent Laid-open No. 264843/1997 discloses measuring cells for a surface plasmon resonance biosensor.
SUMMARY OF THE INVENTION
The present inventors have now found that sensitivity of a measuring chip for a surface plasmon resonance sensor is extremely improved when only a small amount of a physiologically active substance is immobilized on a specific plasma polymerization layer.
An objective of the present invention is to provide a measuring chip for a surface plasmon resonance sensor that can detect a small amount of target substances in high sensitivity.
Another objective of the present invention is to provide a measuring cell for a surface plasmon resonance sensor that can detect a small amount of target substances in high sensitivity.
Further objective of the present invention is to provide a method for producing said measuring chip.
The present invention provides a measuring chip for a surface plasmon resonance sensor comprising a metal layer and one or more plasma polymerization layers formed on said metal layer.
The present invention also provides a measuring chip for a surface plasmon resonance sensor comprising a metal layer, one or more plasma polymerization layers formed on said metal layer, and a biologically active substance immobilized on the surface of said plasma polymerization layer.
The present invention also provides a measuring cell for a surface plasmon resonance sensor comprising said measuring chip.
The present invention also provides a method for producing a measuring chip for a surface plasmon resonance sensor comprising the steps of forming a metal layer on an optically transparent substrate, forming one or more plasma polymerization layers on said metal layer, and then immobilizing a biologically active substance on the surface of said plasma polymerization layer.
REFERENCES:
patent: 5341215 (1994-08-01), Seher
patent: 5494829 (1996-02-01), Sandstrom et al.
patent: 5876753 (1999-03-01), Timmons et al.
patent: 5976466 (1999-11-01), Ratner et al.
patent: 9-264843 (1997-10-01), None
R. Nakamura, et al., Analytical Chemistry, vol. 69, No. 22, pps. 4649-4652, “A Plasma-Polymerized Film for Surface Plasmon Resonance Immunosensing,” Nov. 15, 1997.
H. Yasuda, Academic Press Inc., pp. 77 & 111, “Plasma Polymerization,” 1985.
Patent Abstracts of Japan, vol. 015, No. 398 (C-0874), Oct. 9, 1991, JP 03 164195, Jul. 16, 1991.
Karube Isao
Muguruma Hitoshi
Nagata Ryohei
Nakamura Hiroyuki
Nakamura Runa
DAI Nippon Printing Co., Ltd.
Marschel Ardin H.
Oblon & Spivak, McClelland, Maier & Neustadt P.C.
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