Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving virus or bacteriophage
Reexamination Certificate
1998-12-17
2003-06-17
Le, Long V. (Department: 1641)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving virus or bacteriophage
C435S817000, C435S176000, C435S041000, C435S007210, C435S004000, C435S006120, C435S288200, C435S291400, C436S805000, C436S525000, C436S164000, C436S807000, C436S518000, C250S461100, C250S461200, C422S051000, C422S051000, C422S051000, C422S051000, C422S069000, C422S082110, C427S169000, C427S430100, C427S162000, C427S409000, C427S410000, C427S435000, C205S777500
Reexamination Certificate
active
06579673
ABSTRACT:
TECHNICAL FIELD
The present invention is generally in the field of detecting analytes in a medium and, more particularly, the present invention relates to micro-contact printing of antibody-binding proteins onto a substrate for the development of single use, disposable sensors to indicate the presence of the analyte in a medium.
BACKGROUND OF THE INVENTION
There are many systems and devices available for detecting a wide variety of analytes in various media. Most of these systems and devices are relatively expensive and require a trained technician to perform the test. There are many cases where it would be advantageous to be able to rapidly and inexpensively determine if an analyte were present. What is needed is a biosensor system that is easy and inexpensive to manufacture and is capable of reliable and sensitive detection of analytes, including smaller analytes. Additionally, what is needed is an easy flexible method of preparation of the biosensors which would permit optimum scale-up processing.
Sandstrom et al., 24
Applied Optics
472, 1985, describe use of an optical substrate of silicon with a layer of silicon monoxide and a layer of silicon formed as dielectric films. They indicate that a change in film thickness changes the properties of the optical substrate to produce different colors related to the thickness of the film. The thickness of the film is related to the color observed and a film provided on top of an optical substrate may produce a visible color change. The authors indicate that a mathematical model can be used to quantitate the color change, and that “[c]alculations performed using the computer model show that very little can be gained in optical performance from using a multilayer structure . . . but a biolayer on the surface changes the reflection of such structures very little since the optical properties are determined mainly by the interfaces inside the multilayer structure. The most sensitive system for detection of biolayers is a single layer coating, while in most other applications performance can be by additional dielectric layers.”
Sandstrom et al., go on to indicate that slides formed from metal oxides on metal have certain drawbacks, and that the presence of metal ions can also be harmful in many biochemical applications. They indicate that the ideal top dielectric film is a 2-3 nm thickness of silicon dioxide which is formed spontaneously when silicon monoxide layer is deposited in ambient atmosphere, and that a 70-95 nm layer silicon dioxide on a 40-60 nm layer of silicon monoxide can be used on a glass or plastic substrate. They also describe formation of a wedge of silicon monoxide by selective etching of the silicon monoxide, treatment of the silicon dioxide surface with dichlorodimethylsilane, and application of a biolayer of antigen and antibody. From this wedge construction they were able to determine film thickness with an ellipsometer, and note that the “maximum contrast was found in the region about 65 nm where the interference color changed from purple to blue.” They indicate that the sensitivity of such a system is high enough for the detection of protein antigen by immobilized antibodies. They conclude “the designs given are sensitive enough for a wide range of applications. The materials, i.e., glass, silicon, and silicon oxides, are chemically inert and do not affect the biochemical reaction studied. Using the computations above it is possible to design slides that are optimized for different applications. The slides can be manufactured and their quality ensured by industrial methods, and two designs are now commercially available.
U.S. Pat. No. 5,512,131 issued to Kumar et al. describes a device that includes a polymer substrate having a metal coating. An antibody-binding protein layer is stamped on the coated substrate. The device is used in a process for stamping or as a switch. A diffraction pattern is generated when an analyte binds to the device. A visualization device, such as a spectrometer, is then used to determine the presence of the diffraction pattern.
However, the device described by Kumar et al. has several disadvantages. One disadvantage is that an extra visualization device is needed to view any diffraction pattern. By requiring a visualization device, the Kumar et al. device does not allow a large number of samples to be tested since it is not possible to determine the presence of an analyte by using the unaided eye.
U.S. Pat. No. 5,482,830 to Bogart, et al., describes a device that includes a substrate which has an optically active surface exhibiting a first color in response to light impinging thereon. This first color is defined as a spectral distribution of the emanating light. The substrate also exhibits a second color which is different from the first color (by having a combination of wavelengths of light which differ from that combination present in the first color, or having a different spectral distribution, or by having an intensity of one or more of those wavelengths different from those present in the first color). The second color is exhibited in response to the same light when the analyte is present on the surface. The change from one color to another can be measured either by use of an instrument, or by eye. Such sensitive detection is an advance over the devices described by Sandstrom and Nygren, supra, and allow use of the devices in commercially viable and competitive manner.
However, the method and device described in the Bogart, et al. patent has several disadvantages. One disadvantage is the high cost of the device. Another problem with the device is the difficulty in controlling the various layers that are placed on the wafer so that one obtains a reliable reading. What is needed is a biosensor device that is easy and inexpensive to manufacture and is capable of reliable and sensitive detection of the analyte to be detected.
SUMMARY OF THE INVENTION
The present invention provides an inexpensive and sensitive device and method for detecting analytes present in a medium. The device comprises a biosensing device having a substrate, preferably a metalized polymer film, upon which is printed a specific predetermined pattern of antibody-binding proteins such as Protein A or Protein G. Subsequent exposure to the antibody specific for the desired analyte results in patterned deposition of this antibody. Overall, this allows a modular production format such that large rolls of patterned protein may be made for use with different analytes. Then as needed, the final product may be made by exposure to the necessary antibody.
Upon attachment of a target analyte, which is capable of scattering light, to select areas of the polymer film upon which the protein and antibody are patterned, diffraction of transmitted and/or reflected light occurs via the physical dimensions and defined, precise placement of the analyte. A diffraction image is produced which can be easily seen with the eye or, optionally, with a sensing device.
The present invention utilizes methods of contact printing of patterned, antibody-binding proteins. These proteins bind to antibodies to pattern them on the surface as well as maintain the optimum orientation for the receptor antibodies. The receptor antibodies are specific for a particular analyte or class of analyte, depending upon the protein used. Methods of contact printing which would be useful in generating the sensing devices used in the present system are disclosed fully in U.S. patent application Ser. Nos. 08/707,456, now U.S. Pat. No. 6,020,047 and 08/769,594, now U.S. Pat. No. 6,048,623, both of which are incorporated herein by reference in their entirety. However, since these methods relate to self-assembling monolayers, the methods need to be altered slightly, as discussed below, to print the antibody-binding protein material as this material is not self-assembling.
Patterned antibody-binding protein layers with bound antibodies cause patterned placement or binding of analytes thereon. The biosensing devices of the present invention produced thereby may b
Everhart Dennis S.
Kaylor Rosann M.
McGrath Kevin
Cook Lisa V.
Kilpatrick & Stockton LLP
Le Long V.
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