Physical, Chemical, and Genetic Techniques for Diatom Frustule Modification: Applications in Nanotechnology  
[PERSON]  
1 Institute of Biosciences and Bioresources, National Research Council, Via P. Castellino 111, 80131 Naples, Italy; [EMAIL_ADDRESS]
2 Department of Integrative Marine Ecology, Stazione Zoologica Anton Dohrn, 80121 Naples, Italy;
3  
[PERSON]  
4 Correspondence: [EMAIL_ADDRESS]  
November 5, 20213 December 2  
silica shell whose ordered morphology initially induced the first observer of diatoms (an anonymous English country nobleman of the early XVIII century [5,6]) to question if they were crystals or plants. Frustule silica structure is developed within a cellular compartment called silica deposition vesicle (SDV) [4,9] and its formation is mediated under strict genetic regulation by a series of proteins and other organic compounds (e.g., silaffins, frustulins, cingulins, long chain polyamines), which control and direct silica precipitation, growth and spatial distribution [10].  
Frustules seem to fulfill at least four main functions: mechanical stability (the presence of pores and ridges lower the average stress concentration on the structure allowing the frustule to resist to pressures ranging from 1 to 7 N/mm\({}^{2}\), equivalent to 100-700 t/m\({}^{2}\)[11]); filtering of noxious agents (e.g., separation of nutrients from viruses) [12,13]; sinking speed lowering, allowing for a longer stay of diatoms near ocean surface and, consequently, a longer exposition to sunlight [14]; efficient coupling with sunlight to optimize photosynthesis [15].  
Diatom cultures can be viewed as near-zero cost \"living nanofactories\", being able to produce at high rate and on a large scale three-dimensional nanostructures whose complexity can be hardly reproduced even by the most advanced lithographic techniques. It is not surprising, thus, that in the last 20 years a plethora of applications exploiting diatom frustules and their unique properties have been envisaged and tested in different fields such as optoelectronics [16], plasmonics [17], catalysis [18], biochemical sensing [19], solar energy harvesting [20], biomedicine and drug delivery [21], to name a few, all contributing to what we can define as diatom nanotechnology [22]. In many of these applications, frustule composition needs to be modified in order to obtain the desired functionalities. In general, frustule modification allows broadening the range of potential uses of the material.  
In the present review article, the main physical and chemical techniques aimed at frustule modification are summarized, with indication of some of the relative applications that can be derived. The frontier of frustule modification is represented by the possibility to obtain, by means of the most recent genetic engineering techniques, mutants with a desired frustule morphology for a specific application. The first attempts to reach this goal are reviewed. In general, this overview is focused on intact frustules since we are interested in the exploitation of its complete morpholgy, geometry and characteristic symmetries. The use of diatomic (sedimentary powder derived by fossilized diatoms), e.g., in drug delivery and teranostics, deserves a deep, separate discussion that is beyond the scope of our study.