arcodes are a part of our everyday life. You see them in the grocery store, on letters from the post office, and on DVDs you check out from the video store. Fast, simple, and accurate, barcoding has become the most popular data-entry method to track the ever-exploding amount of information in the macroscopic world in the past 15 years. In the meantime, an increasing demand for tracking smaller items and for direct monitoring of individual chemical interactions has driven the exploration for novel methods of barcoding at much smaller scales (1-4). Successful demonstrations of micro-or nano-sized barcodes in molecular interaction studies (4, 5), combinatorial screening (6), and convert tracking (7 ) have opened up new opportunities for research. This article will introduce recent developments in the field of encoded micro-or nano-sized freestanding particles and various applications. Detailed discussions of other encoding methods, such as molecular tags (8, 9) and non-particle-based platforms (10,11), are beyond the scope of our discussion. Readers who are interested in gaining an in-depth understanding of the field are referred to more comprehensive review papers.A conventional macroscopic barcode is a series of vertical lines ("the bars") and spaces of different widths. Various combinations of bars and spaces represent different characters incorporated in the code. Theoretically, varying the widths, sequential order, and total number of bars and spaces in the barcode can generate an unlimited number of codes. To achieve similar coding capacity at the nanoscale, the right elements to make up the codes (i.e., the bars and spaces) must first be identified. Two criteria are often used in the search for proper elements with distinctive attributes: They must be mixable at

We report here a simple method to generate ordered nanocavity arrays on a Si wafer and use it in surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS). A close-packed SiO2 nanosphere array was first deposited on a low-resistivity Si wafer using a convective self-assembly method. The nanoparticle array was then used as a mask in a reactive ion etching (RIE) process to selectively remove portions of the Si surface. Subsequent sonication removed those physically adsorbed SiO2 nanoparticles and exposed an ordered nanocavity array underneath. The importance of this approach is its capability of systematically varying surface geometries to achieve desired features, which makes detailed studies of the impacts of surface features on the desorption/ionization mechanism feasible. We demonstrated that the in-plane width and out-of-plane depth of the cavities were adjustable by varying etching times, and the intercavity spacing was controllable by varying the number of particle layers deposited. MS detection of small peptides on these substrates showed comparable sensitivity to conventional porous Si substrates (DIOS, desorption/ ionization on porous silicon). The desorption and ionization efficiency of these roughened surfaces exhibited a nonmonotonic relationship to the increased total surface area. Several possible factors contributing to the observed phenomenon are speculated upon. The application of this arrayed surface in metabolite detection of Arabidopsis thaliana root extracts is also demonstrated.