Chemistry: molecular biology and microbiology – Apparatus – Including measuring or testing
Reexamination Certificate
1997-06-03
2001-05-15
Warden, Jill (Department: 1743)
Chemistry: molecular biology and microbiology
Apparatus
Including measuring or testing
C422S082050, C422S105000
Reexamination Certificate
active
06232114
ABSTRACT:
TECHNICAL FIELD
The present invention generally relates to multi-well plates and platforms made with cycloolefins for use in spectroscopic measurements and methods of making such devices. Multi-well plates and platforms are particularly useful for fluorescence measurements of chemical or biological samples.
INTRODUCTION
A number of multi-well plates are commercially available for culturing cells or performing chemical or cellular assays. While many of these multi-well plates offer the desirable features of biocompatibility, ease of manufacture and substantial structural integrity, the inventors of the present invention have generally found that these plates, especially plates with polymeric bottoms, suffer from a substantially high degree of fluorescence. The relatively high amount of background fluorescence inherent in commercially available plates with polymeric bottoms makes such plates generally not suitable for highly sensitive fluorescence measurements associated with many assays, particularly assays of microliter volumes or less.
The inventors of the present invention recognized a need in the chemical and biological arts for multi-well plates and platforms for chemical or biological events, such as binding assays or cell-based assays. The inventors prepared selection criteria for suitable materials for manufacturing multi-well plates and platforms for such applications. As a key example of the selection criteria, which is more fully described herein, the inventors investigated the spectral properties of various polymers, including their fluorescence and transmittance, for compatibility with spectroscopic measurements of chemical and biological events. Such materials would also desirably, but not necessarily depending on the application, have biocompatibility, relative chemical inertness, sufficient rigidity for the application at hand and ease of manufacture. The inventors selected a variety of polymers for testing based, in part, on the structural features of the polymers, which is more fully described herein. The inventors' search for polymers included searching fields not associated with spectroscopic measurements, including arts associated with cycloolefin polymers, such as the electronics and audio recording arts. The inventors compared a variety of materials to fused silica sheets (e.g.glass) that have relatively minor inherent fluorescence. Out of a number of films tested, the inventors surprisingly found cycloolefin films to possess the fluorescence and transmittance properties that approach (or even out perform) that of fused silica glass.
As described herein the inventors for the first time have developed novel multi-well plates using cycloolefins that offer excellent performance characteristics in assays. Such multi-well plates can be used in conventional 96-well plates or higher density formats, such as 384 wells per plate. The inventors also describe herein for the first time novel platforms that can be used for assays or reaction sites that are particularly amendable to manufacture with cycloolefins. Such plates and platforms may also be used for other applications such as diagnostics or synthesis of chemicals.
SUMMARY
The present invention includes devices for spectroscopic measurements, such as multi-well plates and platforms. Typically, such devices comprise a layer of low fluorescence and high transmittance, comprising a cycloolefin polymer, and either a well(s) of a multi-well plate or a platform to hold the layer.
Multi-well plates of the invention comprise a layer of low fluorescence and high transmittance, comprising a cycloolefin polymer, and a well(s) to hold, or form, the layer. The cycloolefin usually comprises at least a portion of a bottom surface of a well of the multiwell plate.
Platforms of the invention comprise a layer, or window, of low fluorescence and high transmittance, usually comprising a cycloolefin polymer or other low fluorescence material, and a scaffolding or frame to hold, or form, the layer. The window has a predetermined dimension and can be arranged as a plurality of windows on the frame in any geometric arrangement, including two-dimensional arrays. In some embodiments the window permits detection of spectroscopic events, where light often passes through the window. In other embodiments the window is basically a reaction or assay site that can permit detection of a chemical reaction or assay.
The invention also includes methods for detection and manufacturing that relate to multi-well plates and platforms of the invention.
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Coassin Peter J.
Harootunian Alec Tate
Pham Andrew A.
Tsien Roger Y.
Aurora Biosciences Corporation
Gray Cary Ware & Freidenrich
Haile Lisa A.
Warden Jill
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