Halogen-modified silicon, surfaces

Details Halogen-modified silicon, surfaces Halogen-modified silicon, surfaces

2001-01-26

2004-02-10

McGarry, Sean (Department: 1635)

Synthetic resins or natural rubbers -- part of the class 520 ser

Synthetic resins

From silicon reactant having at least one...

C536S023100

Reexamination Certificate

active

06689858

ABSTRACT:

FIELD OF THE INVENTION
The invention is directed to modified carbon, silicon, and germanium surfaces (including modified surfaces of alloys containing any combination of carbon, silicon and/or germanium). Specifically, the invention is directed to unoxidized, bromine- or iodine-terminated carbon, silicon, and germanium surfaces modified to have bonded thereto a linker moiety capable of anchoring various other chemical moieties to the unoxidized surface. These modified surfaces are suitable for the fabrication of surface-bound chemicals, including surfaces of bound nucleic acids and nucleic acid arrays comprising two or more such surfaces.
DESCRIPTION OF THE PRIOR ART
Surfaces suitable for the immobilization of nucleic acids have become an increasingly important biological tool in recent years. Arrays of nucleic acid molecules, either as double-stranded segments or as short, single-stranded oligonucleotides, have been utilized for drug development, genetic sequencing, medical diagnostics, nucleic acid-ligand binding studies and DNA computing.
1-21
The principal advantages of using surface-bound oligonucleotides over those in solution include ease of purification, conservation of material and reagents, reduction of interference between oligonucleotides, and facilitated sample handling.
12
Previously explored surfaces for immobilization of nucleic acids include latex beads,
5
polystyrene,
1
carbon electrodes,
22-25
gold,
17,23,26-28
and oxidized silicon or glass.
3,8,11,29-32
The surface chemistries involved with these substrates, however, do not possess many of the desired characteristics of an ideal surface. These ideal surface characteristics include: surface flatness and homogeneity; control of surface properties; thermal and chemical stability, reproducibility; and amenability to nucleic acid immobilization and biochemical manipulation. More recently, the desire to use immobilized nucleic acid as a biosensor in integrated circuits
33
would require a surface amenable to integration into a microelectronics format. The limitations of the prior art surfaces and attachment chemistries indicate a need for alternative substrates that more closely resemble the ideal. As described herein, unoxidized crystalline carbon, silicon, and germanium, allotropes thereof, and alloys thereof offer advantages as substrates for immobilization of nucleic acids and other chemicals having similar or analogous reactivity because of their high purity, highly organized and defined crystalline structure and robustness. Silicon is particularly preferred due to its ubiquitous use in the microelectronics industry.
However, native silicon surfaces, for example, react with air under ambient conditions to form a thin surface layer of silicon oxide. This oxidized silicon surface is chemically similar to glass and suffers from some of the same drawbacks, namely inhomogeneity and variability in the relative number of Si—O—Si and Si—OH linkages. This inhomogeneity and the concomitant chemical variability it engenders can lead to difficulties in the reproducibility and homogeneity of the subsequent chemical-modified surfaces, particularly as the silane chemistry generally employed to couple to such surfaces is itself prone to stability problems and difficult-to-control polymerization processes.
34,35
Chemical pathways for direct functionalization of silicon substrates without an oxide layer have opened up new possibilities for highly-controlled nucleic acid attachment. These new attachment methods provide modified silicon surfaces through direct carbon-silicon bonds,
19,36-42
and have resulted in methyl-, chlorine-, ester-, or acid-terminated substrates.
36,39,40,43,44
Although Wagner et al.
19
describe using an N-hydroxysuccinimidyl ester-terminated silicon surface to immobilize a 1752 bp double-stranded section of DNA, this reference does not disclose a systematic, reproducible method to produce chemically-modified silicon surfaces in general, nor nucleic acid-modified silicon surfaces in particular.
Reactions of &ohgr;-alkenes with silicon surfaces have been described in the prior art, either mediated by diacyl peroxides,
36
through UV irradiation,
19,41
or by direct thermal activation.
39
The &ohgr;-alkenes used have contained a variety of functional groups, including esters, acids,
39,44
and chlorides.
36
The use of halogens as chemical passivating agents for silicon-based semiconductors has been described previously.
52,53
U.S. patent application Ser. No. 09/659,442, filed Sep. 8, 2000, describes a method of creating modified carbon, silicon, and germanium surfaces. The method includes reacting a straight, branched, or cyclic alkene having a substitutent thereon with an unoxidized carbon, silicon, or germanium substrate to yield a modified substrate having bonded directly thereto, in the absence of any intervening oxygen atoms, substituted alkyl moieties. The reaction involves a hydrogen-terminated surface. The strength of a Si—H bond, however, is a good deal larger than either a Si—Br or Si—I bond. Thus, as described in this prior application (to which the subject application claims priority), a photoinitiated reaction designed to break Si—H bonds must use ultraviolet (UV) radiation. Ultra-violet irradiation, however, can damage many samples, including biological samples and other molecular systems that are sensitive to degradation by short-wave light or energetic particles.
SUMMARY OF THE INVENTION
The invention is directed to a method of creating modified carbon, silicon, and germanium surfaces comprising reacting a straight, branched, or cyclic alkene having a substitutent thereon with a bromine- or iodine-terminated carbon, silicon, or germanium substrate to yield a modified substrate having bonded directly thereto, in the absence of any intervening oxygen atoms, substituted alkyl moieties.
A preferred embodiment of the invention is directed to a method of creating modified surfaces on unoxidized, bromine- or iodine-terminated carbon, silicon, and germanium surfaces (iodine being preferred), the method comprising first reacting an amino-, carboxy-, or thiol-modified and protected alkene with a bromine- or iodine-terminated carbon, silicon, or germanium substrate to yield a surface of protected, amino-, carboxy-, or thiol-modified alkane molecules covalently bonded to the substrate in the absence of any intervening oxygen molecules. Then the modified alkane molecules of the first step are deprotected (if necessary), thereby yielding a surface of unprotected modified alkane molecules bonded to the substrate. Next, if necessary, the deprotected modified alkane molecules are reacted with a crosslinker, whereby the crosslinker is attached to the modified alkane molecules. Lastly, molecules such as nucleic acids or proteins are attached to the crosslinker of the previous step, thereby yielding a surface of molecules immobilized on the substrate.
A particularly preferred embodiment of the invention is a method of creating modified surfaces on unoxidized carbon, silicon, and germanium surfaces. The method comprises the following steps: First, reacting iodine with an unoxidized carbon, silicon, or germanium substrate to form an iodine-terminated carbon, silicon, or germanium substrate. Then placing an amino-, carboxy-, or thiol-modified alkene upon the iodine-terminated carbon, silicon, or germanium substrate. The amino-, carboxy-, or thiol-modified alkene of step (b) is then exposed to visible light such that the iodine is removed from the substrate and the amino-, carboxy-, or thiol-modified alkene reacts with the substrate to yield a surface of amino-, carboxy-, or thiol-modified alkane molecules covalently bonded to the substrate in the absence of any intervening oxygen molecules. The modified alkane molecules are then reacted with a crosslinker, whereby the crosslinker is attached to the modified alkane molecules. Lastly, molecules, such as DNA or RNA, are attached to the crosslinker, thereby yielding a surface of molecules immobilized on the substrate.
Because the reaction of the modifie

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