Functional Monolayers for Improved Resistance to Protein Adsorption:  Oligo(ethylene glycol)-Modified Silicon and Diamond Surfaces

Abstract

The interaction of proteins with semiconductors such as silicon and diamond is of great interest for applications such as electronic biosensing. We have investigated the use of covalently bound oligo(ethylene glycol), EG, monolayers on diamond and silicon to minimize nonspecific protein adsorption. Protein adsorption was monitored by fluorescence scanning as a function of the length of the ethylene glycol chain (EG3 through EG6) and the terminal functional group (methyl- versus hydroxyl-terminated EG3 monolayer). More quantitative measurements were made by eluting adsorbed avidin from the surface and measuring the intensity of fluorescence in the solution. The attachment chemistry of the tri(ethylene glycol) molecules and monolayer orientation was studied by X-ray photoelectron spectroscopy. Improvement in the selectivity of surfaces modified with EG functionality was demonstrated in two model biosensing assays. We find that high-quality EG monolayers are formed on silicon and diamond and that these EG3 monolayers are as effective as EG3 self-assembled monolayers on gold at resisting nonspecific avidin adsorption. These results show promise for use of silicon and diamond materials in many potential applications such as biosensing and medical implants.

Surface functionalization of thin-film diamond for highly stable and selective biological interfaces

“…The high chemical stability of diamond has been demonstrated previously when covalently linked to DNA oligonucleotides (22,32) and when functionalized with EG oligomers for protein resistance (40). However, no previous study has examined stability of proteins covalently linked to diamond surfaces.…”

“…Previous studies of protein-resistant monolayers have focused primarily on selfassembled monolayers on gold (6,(13)(14)(15)(16)(17)(18) or silane chemistry (16,39). We recently used fluorescence methods to show that EG6 oligomers bound to diamond surfaces were also highly effective at resisting protein binding (26,40). However, comparisons of different materials or different morphologies are difficult to quantify by this approach because fluorescence quenching can vary substantially between different substrates.…”

“…For these measurements we used avidin as a model system because of its simpler morphology (compared with the highly elongated and variable structure of fibrinogen, for example) and because in previous work we validated the use of a fluorescence wash-off method to quantify the nonspecific binding of avidin (40). After exposing the surface of interest to fluorescently labeled avidin under a given set of conditions the nonspecifically adsorbed material can be digested and released from the surface into solution for quantitative fluorescence measurements.…”

“…This procedure avoids problems of surface-initiated fluorescence quenching. Complete removal from the surface during the digestion can be easily validated experimentally (40). Fig.…”

Click Chemistry‐Based Functionalization on Non‐Oxidized Silicon Substrates

“…[63][64][65][66] Direct photoor thermal-mediated grafting of OEG-terminated alkenes onto an Si À H surface through Si À C bond formation has been reported. [67][68][69] As the OEG-alkenes (e.g., TMG-EG10 in Scheme 8) are hygroscopic and very likely to trap a trace amount of water that is reactive to the Si À H surface under UV irradiation, the photo-initiated grafting must be carried Scheme 7. Formation of an alkyne-presenting monolayer on a non-oxidized silicon substrate through the hydrosilylation of 1,8-nonadiyne and the subsequent functionalization by CuAAC click chemistry.…”