Rapid and accurate diagnosis for pathogens and their antibiotic susceptibility is critical for controlling bacterial infections. Conventional methods for determining bacterium's sensitivity to antibiotic depend mostly on measuring the change of microbial proliferation in response to the drug. Such “biological assay” inevitably takes time, ranging from days for fast-growing bacteria to weeks for slow-growers. Here, a novel tool has been developed to detect the “chemical features” of bacterial cell wall that enables rapid identification of drug resistant bacteria within hours. The surface-enhanced Raman scattering (SERS) technique based on our newly developed SERS-active substrate was applied to assess the fine structures of the bacterial cell wall. The SERS profiles recorded by such a platform are sensitive and stable, that could readily reflect different bacterial cell walls found in Gram-positive, Gram-negative, or mycobacteria groups. Moreover, characteristic changes in SERS profile were noticed in the drug-sensitive bacteria at the early period (i.e., ∼1 hr) of antibiotic exposure, which could be used to differentiate them from the drug-resistant ones. The SERS-based diagnosis could be applied to a single bacterium. The high-speed SERS detection represents a novel approach for microbial diagnostics. The single-bacterium detection capability of SERS makes possible analyses directly on clinical specimen instead of pure cultured bacteria.

A combined process of electropolishing, focused-ion-beam lithography, and controlled anodization is used to fabricate anodic alumina films with ordered nanochannels. The ion beam is used to create a hexagonally close-packed lattice of concaves on a polished aluminum surface and the concaves act as pinning points for guiding the growth of nanochannels in the following anodization step. By carefully matching the lattice constant (100 nm) with the anodization voltage, ordered nanochannels with aspect ratio of ∼100 are fabricated. The effects of the ion dose and its corresponding depth of the concaves on the ordering of the nanochannel array are investigated and a minimum depth of 3 nm is found to be necessary for effective guidance of the growth of ordered nanochannels.