摘要：Whether the aim is to merely prevent the adsorption and accumulation of biological species, or to inhibit the surface-mediated activation of potentially harmful biological processes, biomaterial research invariably faces the need for man-made, foreign surfaces intimately contacting bodily fluids/tissues to be 'bioinert'. A popular strategy to address this technological constraint consists in passivating substrate materials with an antifouling (respectively a biocompatible) organic coating. Yet, despite tremendous research activity and progress in recent times, efficient adlayers are scarce, and endowing artificial surfaces with such properties remains, in essence, a difficult task. This PhD Thesis describes recent research contributions in the development of original and versatile stealth coatings, based on novel oligoethylene glycol trichlorosilane surface chemistry, for bioanalytical and biomedical healthcare applications. Surface modification also has the advantage of being straightforward, rapid and inexpensive. One primary objective was to engineer biosensors capable of selectively and sensitively detecting target analytes in real-world biofluids – exploiting the transducing technology of the ultra-high frequency electromagnetic piezoelectric acoustic sensor (EMPAS) system – as potential clinical assay alternatives to current screening/diagnostic tests. Biosensing platforms featured dual-functional, binary organosilane surface chemistry on quartz combining high analyte binding capability (for biorecognition) with pronounced antifouling properties (to minimize the otherwise overwhelming interference signal from the biological matrix). Clinical testing performance was successfully demonstrated through the detection of bacterial endotoxin – a potent pathogen associated with the highly-incident, deadly condition of sepsis. EMPAS measurements performed in full human blood plasma (and in a real-time and label-free advanced fashion compared to modern clinical assays that rely on chromogenic reporter molecules) showed that samples at abnormally high concentration (1000 pg/mL) can be readily differentiated from those presenting basal endotoxin level (< 10 pg/mL).
Unimolecular, subnanometric silane adlayers featuring a single type of ultrashort monoethylene glycol-terminated chains (MEG-OH) also displayed pronounced antifouling behaviour, against full serum. Further experimental and computational studies collectively corroborated the mechanistic hypothesis according to which water would play a critical role in this respect – through the formation of a permeant, tightly coordinated hydration network, whose disturbance by foulants was rationalized to constitute a penalty in terms of energy and generate repulsive forces. Another major finding was the key participation of the single, internal ether atom of oxygen in the MEG chains in maintaining such a stable, nanoscale zone of hydration. The scope of derivatizable substrate materials of biotechnological importance was also readily expanded to gold (with adapted thiol anchoring chemistry) and polycarbonate polymer. In the latter work with plastic, the unique MEG-OH 'nanogel' ultrathin surface chemistry was also shown to display remarkable antithrombogenic properties, far exceeding those of the bare plastic substrate. More importantly, thrombus growth was nearly non-existent. Such performance was quite outstanding considering the fact that whole human blood did not require any anticoagulant treatment to prevent clotting (besides its standard collection and storage in heparinized tubes) despite being exposed to a foreign surface, in vitro.