**5. Lab-on-paper devices**

Lab-on-paper is a novel technology for fabricating simple, low-cost, portable, and disposable analytical devices holding great promise to aid global health, food quality control, and environmental monitoring [81, 100–105]. Lab-on-paper technology requires minimum fluid samples, compared to common devices, and the porous structure of the paper is solely responsible for fluid transportation. This is a crucial aspect of the diagnostic apparatus, since the substrate must facilitate the diffusion and flow of the solutions within the hydrophilic fiber matrix. The movement of fluids is governed by capillary forces, thus without the need for pumps or power [102, 103]. This technology was introduced in 2007 by Martinez et al. [106] as a method for patterning paper to create well-defined, millimeter-sized channels comprising hydrophilic paper bounded by hydrophobic polymer; but the first evidence of the lab-on-paper technology dates back to 1902 with a patent for paper strips impregnated with hydrophobic materials [107]. Earlier diagnostic applications of lab-on-paper comprise the detection of nickel and copper salt concentrations [108], determination of pH for water testing and biological analysis of urine and blood composition [109].

To date, researchers have been focused on adapting new developments in nanotechnology, biotechnology, and materials science to paper-based sensors. The production of practical analytical devices, based on those developments and by simple fabrication techniques, can have a positive impact for creating worldwide applications where they are most needed [100, 104, 106, 110, 111].

The fabrication of lab-on-paper devices starts by defining channels and reaction zones onto paper, in order to control the movement of liquids and to assure the confinement of different reagents. A wide range of diverse patterning techniques was already reported and can be divided in three major patterning principles: (i) physical blocking of pores in paper (e.g., photolithography [106], plotting [112], and laser treatment [113]); (ii) physical deposition of reagent on fiber surface (e.g., inkjet etching [114] and wax printing [104, 115]); and (iii) chemical modification of fiber surface (e.g., plasma treatment [116], inkjet printing [117], and silanization [118]). Each technique has its advantages and limitations which have to be taken under consideration according to the type of device, equipment available, material costs, and the intended application, among other factors.
