Chemistry: analytical and immunological testing – Involving an insoluble carrier for immobilizing immunochemicals – Carrier is inorganic
Reexamination Certificate
1997-06-25
2002-04-09
Venkat, Jyothsna (Department: 1627)
Chemistry: analytical and immunological testing
Involving an insoluble carrier for immobilizing immunochemicals
Carrier is inorganic
C426S578000, C426S523000, C426S524000, C426S521000, C426S521000, C426S521000, C426S521000, C426S530000, C426S531000, C435S176000, C435S177000, C530S326000, C530S327000, C530S328000
Reexamination Certificate
active
06368877
ABSTRACT:
BACKGROUND OF THE INVENTION
Organic surfaces have been employed in numerous methods and systems, including as substrates for ELISA, cell and tissue culture. Self-assembled monolayers (SAMS) are a class of organic surfaces manufactured by imprinting a monolayer of organic compounds with reactive moieties onto a solid support under conditions wherein the compounds react with and bind to the solid support in a single ordered and patterned layer. See, Lopez, et al., “Convenient Methods for Patterning the Adhesion of Mammalian Cells to Surfaces Using Self-Assembled Monolayers of Alkanethiolates on Gold,”
J. Am. Chem. Soc.,
115(13):5877-5878 (1993) and Mrksich and Whitesides, “Using Self-Assembled Monolayers to Understand the Interactions of Man-Made Surfaces with Proteins and Cells”,
Annu. Rev. Biophys. Biomol. Struct.,
25:55-78 (1996). Molecular self-assembly is the spontaneous association of molecules under equilibrium conditions into stable, structurally well-defined order joined by non-covalent bonds. SAMs manufactured to date have linked chemical moieties to solid surfaces through long chain alkyl linkages. Examples of organic compounds which have been patterned on a solid support include alkanethiolates and alkylsiloxanes. The SAMs are manufactured employing a process termed “microcontact printing.”
It has been suggested that SAMs can be used to pattern cells on a surface by presenting chemical moieties which bind to the cells on the solid surface. Mrksich and Whitesides, above. However, these molecules, and the resulting SAMs, can be difficult and/or expensive to manufacture. Thus, improvements and cost reductions in the manufacture of SAMs are desirable and are necessary.
SUMMARY OF THE INVENTION
This invention is based upon the discovery that improved SAMs can be manufactured by imprinting reactive self assembling peptides onto solid supports. The SAMs are characterized by ease of manufacture and purification. They are versatile in their ability to readily provide a large variety of chemical reactive moieties, or “presenting groups”, to selected targets. For example, the SAM's of the present invention can be readily designed to present ligands to cellular receptors, cell adhesion motifs, antibodies or antigen-binding fragments thereof to cell surface proteins. This preferred class of SAMs can be used to bind a target, e.g. a selected cell or cells, to a predetermined locus on the solid support.
Thus, the invention relates to a composition of matter comprising a solid support and a self-assembled monolayer of linear peptides wherein said peptides bound directly to said solid support through a terminal amino acid in a predetermined pattern. Preferably, the peptides comprise a terminal reactive group, a central linker and a presenting group. The invention also relates to the uses and applications of the SAMs described herein, as will be described in more detail below.
The invention further relates to a method for manufacturing a SAM, or a composition of matter comprising a solid support and a self-assembled monolayer of linear peptides wherein said peptides bound directly to said solid support through a terminal amino acid in a predetermined pattern, comprising microcontact printing the reactive peptides onto the solid support and maintaining the peptides under conditions suitable for binding.
The foregoing and other objects, features and advantages of the invention will be apparent from the following more particular description of preferred embodiments of the invention, as illustrated in the accompanying drawings. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principals of the invention.
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Rich Alexander
Whitesides George
Yan Lin
Zhang Shuguang
Garcia Maurie E.
Massachusetts Institute of Technology
Venkat Jyothsna
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