# Quantum Leap from Gold and Silver to Aluminum Nanoplasmonics for Enhanced Biomedical Applications
## 3 Applications  
### Biosensing  
In the field of biosensing, Raman, infrared (IR), and fluorescence spectroscopies have been of outstanding importance in understanding the system response to environments at the molecular level. Raman spectroscopy provides excellent vibrational fingerprints for fast chemical identification. Raman microscopic imaging provides a high spatial resolution with chemical sensitivity, which enables the label-free, on-site in vivo analysis of chemical and structural information of a wide range of biological systems. There has been a significant progress in the development of Raman spectroscopy-based techniques for bacterial cell analysis, clinical diagnosis, structural characterization, and detection of biofilms [92; 93; 94; 95; 96; 97; 98; 99]. However, the drawbacks of the spontaneous Raman technique are low sensitivity, particularly for biological samples, and insufficient time resolution due to the long signal accumulation. Plasmonic NSs have been used in surface-enhanced Raman scattering (SERS) [100; 101; 102], and surface-enhanced fluorescence (SEF) [103] to increase the detection sensitivity and speed. These developments stimulated intensive studies of applications in biosensing and optical devices. SERS takes advantage of an electric field enhancement of several orders of magnitude in the vicinity of plasmonic metal NSs. However, the majority of SERS studies used noble metals such as Au and Ag, and only recently were extended to Al, which has an important advantage of SPR tunability in the UV range [104]. While the Au and Ag NSs are significant in biosensing, Al plasmonics provide similar results with high tunability and low cost. Most biosensing studies were also performed separately from the medical treatment, focusing mainly on sensing and species identification, without the systematic analysis of cell viability. Au and Ag NPs were previously used to enhance the Raman signals of bacteria [97; 105; 106; 107]. However, most measurements were performed in laboratory conditions on single bacterial cells dried on a substrate or in solution mixed with plasmonic NPs [108]. The cytotoxicity of the Au and Ag NPs under these conditions has also been poorly understood. The unique plasmonic properties of Al NPs enable promising applications in biosensing via SERS [109; 110; 111] and refractive index measurements [112; 113; 114; 115]. In this review, we discuss the combination of medical treatment and sensing using Al NPs towards the development of inexpensive devices that will lead to new breakthroughs not only in biosensing, but also in other fields such as medical treatment, industrial materials processing, and quality control. Many biomolecules including DNA and proteins have UV resonances, which enable resonance Raman spectroscopy with low fluorescence background [116]. Due to low losses in UV range, Al substrates were used for deep-UV SERS [117], showing several orders of magnitude enhancement for adenine on Al nanovoid substrates (Figure 3c) [118]. Large enhancement factors of resonance Raman signals of biomolecules using aluminum film-over nanosphere (ALFON) substrates were observed (Figure 3d) [119]. Al bowtie nanoantennas showed large UV resonance Raman enhancement in benzene [120]. Similar performance of SERS on Al NSs was shown in one-to-one comparison with Ag and Au [121]. These studies showed successful examples of the combined action of the plasmonic and UV resonance enhancement mechanisms in biosensing. SEF has also been used for the detection of biomolecules. For example, Al substrates may provide effective adenine fluorescence enhancement in the UV spectral range [122]. Weak fluorescence of biomolecules such as proteins and DNA [123; 124; 125] was enhanced by Al NPs [126; 127; 128]. Al nanostructured substrates were used to enhance the fluorescence of proteins with a different number of tryptophan residues (Figure 3a) [129]. The weak intrinsic fluorescence of adenine was enhanced by Al NP arrays upon UV excitation (Figure 3b) [130].