Source: https://patents.google.com/patent/US5457527
Timestamp: 2018-08-18 16:52:31
Document Index: 686834720

Matched Legal Cases: ['art.\n7', 'art.\n8', 'art.\n13', 'art.\n14', 'art.\n16', 'art.\n17']

US5457527A - Microplate forming wells with transparent bottom walls for assays using light measurements - Google Patents
Microplate forming wells with transparent bottom walls for assays using light measurements Download PDF
US5457527A
US5457527A US08220111 US22011194A US5457527A US 5457527 A US5457527 A US 5457527A US 08220111 US08220111 US 08220111 US 22011194 A US22011194 A US 22011194A US 5457527 A US5457527 A US 5457527A
US08220111
Roy L. Manns
Alfred J. Kolb
Bernard S. Effertz
A microplate forms a multiplicity of sample wells for holding samples to be assayed by light emissions or light transmission. The microplate comprises a unitary upper plate and a unitary lower plate. The unitary upper plate forms the side walls of the sample wells, while the unitary lower plate forms the bottom walls of the sample wells. The side walls are opaque so that light cannot be transmitted between adjacent wells through the side walls. The bottom walls are transparent to allow the transmission of light therethrough. Bands of opaque material surround the bottom wall of each well and are located below a level of an upper surface of, the bottom wall of each well. The bands of opaque material are constructed and arranged to block the transmission of light between adjacent wells through the lower plate.
This application is a continuation of application Ser. No. 07/890,030, filed May 28, 1992, now U.S. Pat. No. 5,319,436 and entitled "MICROPLATE FOR ASSAYS USING LIGHT MEASUREMENTS".
The present invention relates generally to multi-well staple trays which are commonly referred to as microplates and which are used to hold a large number (e.g., 24, 48 or 96) of samples to be assayed by various techniques such as scintillation counting, luminometry, kinetics etc. This invention is particularly concerned with microplates for use in assaying techniques which require the emission of light from the sample, as occurs in scintillation counting, fluorimetry and luminometry, or the transmission of light through the sample.
When microplates are used to hold samples to be assayed by techniques which are dependent on light emissions from the sample, it is important to avoid light transmission between adjacent samples, i.e., "crosstalk." Such crosstalk is extremely undesirable because it means that the photons detected in any particular sample well might not have originated from the particular sample in that well, and the purpose of the assaying technique is to obtain a unique measurement for each individual sample that is representative of only that sample.
It is a primary object of the present invention to provide an improved microplate which includes a transparent wall which permits viewing of the sample and/or the measurement of light emissions from the sample, and yet avoids crosstalk between adjacent wells.
FIG. 1 is an exploded perspective view of a microplate embodying the present invention:
While the invention is susceptible to various modifications and alternative form, specific embodiments thereof have been shown by way of example in the drawings and will be described in detail. It should be understood, however, that it is not intended to limit the invention to the particular forms disclosed, but on the contrary, the intention is to cover all modifications, equivalents and alternatives falling within the spirit and scope of the invention as defined by the appended claims.
Turning now to the drawings and referring first to FIG. 1, there is shown a microplate 10 formed from two molded plastic plates 11 and 12. The upper plate 11 forms the side walls 13 of the multiple wells of the microplate, and in the illustrative example the wells are arranged in an 8×12 or 4×6 matrix. The bottom plate 12 forms the bottom walls 14 of the web, and is attached to the lower surface of the upper plate 11 by fusing the two plates together. As will be described in more detail below, the fusion is preferably effected by ultrasonic bonding.
In order to confine light emissions to the well in which they originate, i.e., to prevent light transmission between adjacent wells, the upper plate 11 is formed from an opaque polymeric material so that light cannot be transmitted therethrough. For assaying techniques which require the detection of very small amounts of light, as in liquid scintillation counting, the pigmentation used to render the polymeric material opaque is preferably light in color so as to be highly reflective in order to ensure high counting efficiency with respect to the radioactive samples. To form an opaque light colored plate, a pigment having a high Albedo, preferably white, is added to the resin in an amount from about 2 to about 20 weight percent. If a greater amount of pigment is added, the resin becomes too viscous for injection molding. The white pigment is selected from the group consisting of titanium dioxide, zinc oxide, zinc sulfide and thithopone. Titanium dioxide is generally more chemically resistant to scintillation cocktail solvents.
In certain types of luminescence and fluorescence assays it is preferred that the side walls 13 of the sample wells be non-reflective, in which case the upper plate 11 is preferably formed from a black or dark-colored polymer. The dark polymer may be formed by the addition of carbon black in mounts ranging from about 0.5 weight % to about 15 weight %.
The transparent bottom walls of the wells are desirable in assaying techniques that measure light emitted from, or transmitted through, the sample in each individual well. Examples of such techniques are liquid scintillation counting, which counts light emissions produced by a radioactive sample in a liquid scintillator, and techniques which measure light emitted by luminescent labels, such as bioluminescent or chemiluminescent labels, fluorescent labels, or absorbence labels. These techniques use various types of light detectors, such as one or more photomultiplier tubes per well, solid state imaging devices with either lenses or fiber optic couplers, and fiber optic devices.
For any given assaying technique, the polymeric material chosen to form the plate must be nonreactive with, insoluble in, and impervious to the materials contained in the samples to be used in the assay. One particularly preferred resin is a copolymer containing at least 50 weight percent of an unsaturated nitrile monomer and a second monomer which is capable of being copolymerized with the unsaturated nitrile monomer. These high nitrile resins have excellent transparency, rigidity, processability and gas barrier resistance to oxygen, carbon dioxide and other gases. The resins are highly chemically resistant to solvents such as benzene, toluene, xylene, 1,2,4-trimethylbenzene (pseudocumene), alkobenzenes, diisopropyl napthalene, phenylxylylethane (PxE), heptane and ethyl acetate. One or more of the aforementioned solvents are usually present in liquid scintillation cocktails. Additionally, these resins form a microplate that does not deteriorate when exposed to ultraviolet light during storage.
Preferably, the unsaturated nitrile monomer of the above resins is selected from the group consisting of acrylonitrile and methacrylonitrile. The monomer capable of being copolymerized with the unsaturated nitrile is an ethylenically unsaturated copolymerizable monomer selected from the group consisting of alkyl acrylates, alkyl methacrylates, acrylic acid or methacrylic acid. According to one embodiment of the invention, the resin is a rubber modified acrylonitrile-methylacrylate copolymer containing about 75 weight percent acrylonitrile and about 25 weight percent methylacrylate. Such a rubber modified copolymer resin is commercially available under the trademark Barex 210-I® resin manufactured by British Petroleum Chemicals Corporation.
For the purpose of attaching the two plates 11 and 12 to each other, while at the same time forming an effective said against liquid cross talk, a grid 30 of beads 31 is formed on the top surface of the lower plate 12. A similar grid 32 of grooves 33 is formed in the bottom surface of the upper plate 11 for receiving the bead grid 30. The height of the beads 31 is made substantially greater than the depth of the grooves 33 to ensure that the beads 31 are thoroughly melted to fill the grooves 33. For example, in a preferred embodiment the vertical dimensions of the beads 31 and the grooves 33 are 0.026 inch and 0.007 inch, respectively. With these dimensions, the application of ultrasonic energy thoroughly melts the beads 31.
The preferred ultrasonic bonding process may be effected by applying the energy to the lower plate 12 through a transducer or "horn" having a fiat surface of about the same dimensions as the plate 12, with multiple recesses located in the same regions as the well holes in the upper plate 11. The recesses help to concentrate the ultrasonic energy in the regions between the wells.
1. A microplate forming a multiplicity of sample wells for holding samples to be assayed by light emissions or light transmission, said plate comprising
a unitary upper plate forming the side walls of the sample wells, said side walls being opaque so that light cannot be transmitted between adjacent wells through said side walls,
a unitary lower plate forming the bottom walls of the sample wells, said bottom walls being transparent to allow the transmission of light therethrough, said bottom walls having respective upper surfaces, and
bands of opaque material surrounding the bottom wall of each well and located below a level of the upper surface of the bottom wall of each well, said bands of opaque material constructed and arranged to block the transmission of light between adjacent wells through said lower plate.
2. The microplate of claim 1, wherein said bands of opaque material are disposed in said lower plate.
3. The microplate of claim 1, wherein said bands of opaque material are formed from opaque beads surrounding the bottom wall of each well.
4. The microplate of claim 3, wherein said beads are integrally formed with the lower surface of said upper plate.
5. The microplate of claim 4, further including grooves in the upper surface of said lower plate receiving said beads.
6. The microplate of claim 1, wherein said upper plate is a single molded plastic part.
7. The microplate of claim 1, wherein said lower plate is a single molded plastic part.
8. A microplate forming a multiplicity of sample wells for homing samples to be assayed by light emissions or light transmission, said plate comprising
opaque beads surrounding the bottom wall of each well and located below a level of the upper surface of the bottom wall of each well.
9. The microplate of claim 8, wherein said beads are integrally formed with the lower surface of said upper plate.
10. The microplate of claim 9, further including grooves in the upper surface of said lower plate receiving said beads.
11. The microplate of claim 8, wherein said beads form bands of opaque material surrounding the bottom wall of each well to block the transmission of light between adjacent wells through said lower plate.
12. The microplate of claim 8, wherein said upper plate is a single molded plastic part.
13. The microplate of claim 8, wherein said lower plate is a single molded plastic part.
14. A microplate forming a multiplicity of sample wells for holding samples to be assayed by light emissions or light transmission, said plate comprising
a unitary lower plate forming the bottom walls of the sample wells, said bottom walls being transparent to allow the transmission of light therethrough, and
grooves formed in the upper surface of said lower plate and surrounding the bottom wall of each well, said grooves being filled with opaque material to block the transmission of light between adjacent wells through said lower plate.
15. The microplate of claim 14, wherein said upper plate is a single molded plastic part.
16. The microplate of claim 14, wherein said lower plate is a single molded plastic part.
17. A microplate forming a multiplicity of sample wells for holding samples to be assayed by light emissions or light transmission, said plate comprising
opaque material disposed at a surface of said lower plate between adjacent wells and beneath a level of an upper surface of the bottom wall of each sample well so as to reduce the transmission of light between the adjacent wells through said lower plate.
18. The microplate of claim 17, wherein said opaque material is dark-colored.
19. The microplate of claim 18, wherein said opaque material is black.
US08220111 1992-05-28 1994-03-30 Microplate forming wells with transparent bottom walls for assays using light measurements Expired - Lifetime US5457527A (en)
US07890030 US5319436A (en) 1992-05-28 1992-05-28 Microplate farming wells with transparent bottom walls for assays using light measurements
US08220111 US5457527A (en) 1992-05-28 1994-03-30 Microplate forming wells with transparent bottom walls for assays using light measurements
US07890030 Continuation US5319436A (en) 1992-05-28 1992-05-28 Microplate farming wells with transparent bottom walls for assays using light measurements
US5457527A true US5457527A (en) 1995-10-10
ID=25396133
US07890030 Expired - Lifetime US5319436A (en) 1992-05-28 1992-05-28 Microplate farming wells with transparent bottom walls for assays using light measurements
US08220111 Expired - Lifetime US5457527A (en) 1992-05-28 1994-03-30 Microplate forming wells with transparent bottom walls for assays using light measurements
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Owner name: BANK OF AMERICA NATIONAL TRUST & SAVINGS ASSOC., C
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Free format text: SECURITY INTEREST;ASSIGNORS:PACKARD BIOSCIENCE COMPANY (DE CORPORATION);PACKARD INSTRUMENT COMPANY,INC. (DE CORPORATION);REEL/FRAME:009289/0270
Owner name: PACKARD BIOSCIENCE COMPANY, CONNECTICUT
Free format text: RELEASE OF SECURITY INTEREST;ASSIGNOR:BANK OF AMERICA TRUST AND SAVINGS ASSOCIATION;REEL/FRAME:015428/0171