Chemistry: molecular biology and microbiology – Apparatus – Including measuring or testing
Reexamination Certificate
2000-11-08
2002-11-19
Whisenant, Ethan C. (Department: 1655)
Chemistry: molecular biology and microbiology
Apparatus
Including measuring or testing
C435S006120, C435S091100, C435S287100, C422S068100, C536S023100
Reexamination Certificate
active
06482638
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to heat-relaxable substrates. More particularly, the present invention provides high density arrays on heat-relaxable substrates, along with methods and apparatus for relaxing substrates using electromagnetic energy.
BACKGROUND
Arrays may be used in a variety of applications, such as gene sequencing, monitoring gene expression, gene mapping, bacterial identification, drug discovery, and combinatorial chemistry. Many of these applications involve expensive and oftentimes difficult to obtain samples and reagents. Accordingly, high density arrays are desirable because the use of such arrays may dramatically increase efficiency with respect to limited or expensive samples when compared to standard arrays, such as a 96 well plate. For example, a 96 well plate may require several hundred microliters of sample per well to run a diagnostic experiment whereas a high-density array would require only a fraction of that sample for the entire array. In addition to the reduction of volume, miniaturization allows hundreds or thousands of tests to be performed simultaneously. Furthermore, a high-density array may be more versatile than a standard array because of the wide variation of chemistries that may be present on a single array.
Problems in the manufacturing of high-density arrays on standard substrates, e.g., glass microscope slides, include the need for multiple steps to produce the arrays with densely packed reactants. The manufacture of high-density arrays is further complicated when different chemistries are required at different binding sites on the arrays, such as required for manufacturing nucleic acid arrays.
Attempts to address the need for high-density arrays have included using oriented polymeric films in place of glass slides as the substrate for the arrays. The arrays can include binding sites formed on the oriented polymeric films in a larger format that is easier to manufacture, after which the oriented polymeric films can be relaxed by applying thermal energy to the substrate to provide arrays with high-density sites. Examples of such arrays are described in WO 99/53319 (HIGH DENSITY, MINIATURIZED ARRAYS AND METHODS OF MANUFACTURING SAME, published Oct. 21, 1999) and commonly assigned U.S. patent application Ser. No. 09/287,379, filed Apr. 7, 1999, entitled HIGH DENSITY, MINIATURIZED ARRAYS AND METHODS OF MANUFACTURING SAME.
Although the oriented polymeric films provide significant advantages in array manufacturing, their use does pose additional problems during the substrate relaxation process. One potential problem is achieving uniform transmission of thermal energy to the array substrate. Another potential problem is curling or other distortion of the substrate during the application of thermal energy to induce relaxation.
Oriented polymeric films used in, e.g., packaging applications, are typically relaxed using thermal energy supplied by air. When used as packaging, however, the flatness of the film after relaxation is typically not important because the film is constrained around a package, typically conforming to the shape of the package. In applications where a flat film is desired after relaxation, the film is typically placed in tension. An example of one such application is in the use of oriented polymeric films over windows to prevent drafts, provide additional insulation, etc. When used on windows, the film is held in tension between, e.g., adhesive tapes applied to the window frame. When provided as the substrate of an array, however, the film is not so constrained or tensioned, thereby causing the potential for curling as described above.
Another issue to address is how to quickly and efficiently supply the thermal energy required to relax the film. The use of conductive heating devices, e.g., hot plates, may require the constant attention of an operator or feedback control systems to prevent overheating and/or uneven heating of the film.
Another concern with heat-relaxable arrays manufactured with attached or embedded materials that make the array useful for bioanalytical applications, e.g., DNA, RNA, proteins, polysaccharides, antibodies, etc., is that the application of excessive thermal or other forms of energy may adversely affect the functional performance of the materials on the array. invention provides articles, such as high density arrays, including heat-relaxable substrates that can be relaxed by exposure to electromagnetic energy. Methods of relaxing arrays including heat-relaxable substrates and reactants affixed thereto are also provided in connection with the present invention. In still other embodiments, the present invention also provides methods of manufacturing such articles, as well as systems and apparatus for relaxing the same using electromagnetic energy.
In some embodiments, the substrates suitable for use in manufacturing arrays may themselves include electromagnetic energy sensitive Curie point material in their construction, in which case exposure of the substrates to suitable electromagnetic energy can provide the thermal energy required to cause the substrates to relax. The substrates may additionally comprise linking agents or masks, in which case the electromagnetic energy sensitive material may be included in the linking agents or masks. Such methods for providing energy may be referred to as direct heating, i.e., no additional apparatus must be supplied to cause the conversion of electromagnetic energy to heat that is used to relax the substrates.
In preferred embodiments, the substrates include a coating of linking agents, with electromagnetic sensitive material included in the substrate. In a most preferred embodiment, arrays include reactants affixed to the substrates.
Substrates that include an electromagnetic energy sensitive material in their construction may also be placed in a system or apparatus that also includes the same or a different electromagnetic energy sensitive material to provide the thermal energy needed to relax the substrate when exposed to electromagnetic energy.
In its various aspects, the present invention provides a convenient manner of relaxing substrates that include heat-relaxable material. The amount of energy supplied to relax the substrates can be easily controlled and the process can be performed quickly and economically.
In preferred embodiments, wherein reactants are affixed to the substrates, additional benefits may be achieved. For example, after relaxation, the resulting high density arrays can provide a level of flatness useful in activating accurate hybridization results.
In another aspect of the invention, methods are provided for relaxing a substrate. In one embodiment, a method includes providing an array including a heat-relaxable substrate and reactants affixed thereto; providing electromagnetic energy sensitive material
In preferred embodiments, wherein reactants are affixed to the substrates, additional benefits may be achieved. For example, after relaxation, the resulting high density arrays can provide a level of flatness useful in achieving accurate hybridization results.
In another aspect of the invention, methods are provided for relaxing a substrate. In one embodiment, a method includes providing an array including a heat-relaxable substrate and reactants affixed thereto; providing electromagnetic energy sensitive material in proximity to the substrate; and directing electromagnetic energy towards the electromagnetic energy sensitive material, wherein the electromagnetic energy is converted into thermal energy and conducted to the heat-relaxable material, thereby causing the heat-relaxable material in the substrate to relax.
In another aspect, the present invention provides apparatus for relaxing heat-relaxable articles. In one aspect, the present invention includes the apparatus having a first surface; a second surface opposed to and spaced from the first surface; and electromagnetic energy sensitive material in thermal communication with the first surface, whereby heating of the electromagnetic energy sensitive mate
Duan Daniel C.
Halverson Kurt J.
LePere Pierre H.
Patil Sanjay L.
3M Innovative Properties Company
Busse Paul W.
Gram Christopher D.
Lu Frank
Sprague Robert W.
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