Microarray technology has been widely used for genomics and proteomics research as well as for drug screening. Currently, the spot size in most microarrays is larger than one micron. The use of nanometric biomolecular arrays, with smaller spot sizes, will enable high-throughput screening of biomolecules—eventually at the single molecule level. Also, nanometric arrays permitting precise control over the position and orientation of individual molecules will become a powerful tool for studying multi-valent and/or multi-component molecular interactions in biological systems. Toward these ends, protein arrays with feature sizes smaller than 100 nm have been fabricated, mostly using dip-pen nanolithography and nanografting. See Lee et al., Science 2002, vol. 295, p. 1702; Wilson et al., Proc. Natl. Acadi Sci. USA 2001, vol. 98, p. 13660; Liu et al., Proc. Natl. Acad. Sci. USA 2002, vol. 99, p. 5165; Pavlovic et al., Nano Lett. 2003, vol. 3, p. 779; and Krämer et al., Chem. Rev. 2003, vol. 103, p. 4367.
Biological microelectromechanical systems (bioMEMS) are of tremendous interest for their potential applications in microscale, high throughput biosensing and medical devices (Shawgo et al., J. Curr. Opin. Solid State Mater. Sci. 2002, v. 6, p. 329). Using silicon as a substrate for the preparation of such devices is particularly attractive, since the extensive micro-fabrication techniques developed by the microelectronic industries can be used to fabricate and integrate various micro-components into the devices. For reducing biofouling, considerable research has been directed to the modification of substrate surfaces with stable and ultrathin films of poly(ethylene glycol) (PEG) or oligo(ethylene glycol) (OEG) (Prime et al., Science 1991, vol. 252, p. 1164). Since many of the ultimate applications for bio-devices require moderate-term (e.g., a few hours to several days) exposure to biological media (e.g., buffer of pH 7.4 at 37° C.), stability of the bio-compatible coatings on the devices under these conditions is highly desirable. All of the OEG/PEG-terminated films on silicon substrates reported by others are bound onto the silicon surfaces via Si—O bonds that are prone to hydrolysis (Calistri-Yeh et al., Langmuir 1996, v. 12, p. 2747), thereby limiting their stability under physiological conditions (Sharma et al., Langmuir 2004, v. 20, p. 348).
As described in commonly assigned, co-pending U.S. patent application Ser. No. 10/742,047, olig(ethylene glycol) (OEG) terminated alkenes were grafted onto hydrogen-terminated silicon surfaces through hydrosilylation (as developed by Linford and Chidsey, see Linford et al., J. Am. Chem. Soc. 1993, v. 115, p. 12631; Buriak, Chem. Rev. 2002, v. 102, p. 1271) forming robust Si—C bonds with the silicon surfaces. It was shown that the alkyl monolayers grown by this method were stable in boiling organic solvents, water, and acids, as well as slightly basic solutions (Linford et al., J. Am. Chem. Soc. 1995, v. 117, p. 3145). A method describing the modification of hydrogen-terminated silicon surfaces, including a silicon atomic force microscopy (AFM) cantilever tip, with OEG-terminated alkenes via either thermally- or photo-induced hydrosilylation is also found in commonly assigned, co-pending U.S. patent application Ser. No. 10/742,047. See also Yam et al., J. Am. Chem. Soc. 2003, v. 125, p. 7498; Yam et al., Chem. Commun., 2004, p. 2510). The efficiency with which such OEG-terminated films resist protein adsorption depends on many factors including the number of ethylene glycol (EG) units and the packing density of the films that is determined by the underlying substrate surface and the deposition methods. For example, OEG-terminated thiolate self-assembled monolayers (SAMs) on gold (111) surfaces are protein resistant, but those on silver (111) surfaces are not (Herrwerth et al., J. Am. Chem. Soc. 2003, vol. 125, p. 9359). The latter was attributed to the high packing density and structural ordering of the SAMs. Research has demonstrated that films grown on Si (111) surfaces had a density similar to that of the corresponding thiolate SAMs on gold (111) surfaces, and similarly reduced the adsorption of fibrinogen to 1% monolayer or less (Cai et al., to be submitted).
As a result of the foregoing, a nanometric biomolecular array comprising a stable, patternable monolayer surface, and an efficient method of making such an array, would be very beneficial.