# Returning to Nature for the Design of Sportive Phases in Solid-Phase Microextraction
## 6 Trends, Natural Products for Simplifying the Analytical Workflow  
The classical analytical workflow comprises the isolation/enrichment of the targets from the sample matrix to obtain a clean extract that is finally analyzed by chromatography. This approach provides a high level of sensitivity and selectivity, but the sample throughput is usually limited by the chromatographic cycle. The elimination of the chromatographic separation, by the direct combination of the microextraction step with the instrumental technique, appears as an attractive alternative. However, avoiding the chromatographic separation compromises the method selectivity, and this loss can be offset by improving the selectivity on the analyte isolation by using a selective instrumental technique such as high-resolution mass spectrometry (MS) or by combining both strategies. [PERSON] and [PERSON] have recently reviewed the potential of the SPME-MS combination promoting as well, changing the classic perspective about chemical analysis [99]. This comprehensive and inspiring review divides this combination into four main groups, depending on the sorptive phase employed namely: fiber/tip, in-tube, mesh, and substrate spray. SPME substrate spray approaches are very versatile, comprising different supports such as coated blades [100; 101; 102], paper [103; 104], or wooden tips [105; 106]. The latter configurations, which make use of natural substrates, are named as paper spray and wooden tip spray, respectively. In both approaches, the substrate can be used for the direct ionization of the sample [107] or the off-line coupling with a microextraction technique [108]. However, the substrate can also be modified with a sorptive phase for the isolation of the target analytes prior to their direct analysis by MS [103]. Although the discussion of the microextraction-MS coupling is beyond the scope of this article, the description of the synthesis of sorptive phases based on paper and wood is relevant and it will be briefly discussed below. The selected developments have been used under the classical or direct analytical workflows. Paper is a cellulose-processed material that shares some of the characteristics of cotton but presents a flat configuration. This geometry opens the door to its application under the thin film microextraction technique. Although bare paper can be used for extraction [109], it is usually modified to boost its extraction capability. This modification can be done by the covalent bonding [110] or by the deposition of a thin layer of sorptive phase [111]. The coating of paper with polymers of both synthetic [112] and natural origins [113] appears as an interesting way to synthesize versatile sorptive phases. Conventional coatings in microextraction, such as PDMS [114], have been recently complemented by other approaches. In 2017, [PERSON] et al. proposed the simple modification of paper by dip coating for the extraction of methadone from biological samples [111]. This process is based on the previous dissolution of a polymer in a volatile solvent and the immersion of paper in this solution. The evaporation of the solvent creates a thin film of the polymer over the paper whose thickness depends on the polymer concentration in the original solution and the number of dips developed during the synthesis. The use of polyamides in combination with a template molecule has been used for the fabrication of molecularly imprinted papers [115]. If some nanoparticles are included in the polymer solution, they can be incorporated into the coating, providing additional characteristics [116]. Also, the dip coating has been proposed to cover paper with a pure film of carbon nanohorn suprastructures that can be used for the extraction of drugs from biological matrices [117]. The SEM micrograph of Figure 3 shows how the dahlias (the ordered aggregates of carbon nanohorns) are combined to form a homogeneous coating over the paper. Wood is a mixture of natural materials such as lignin, cellulose, and hemicellulose [118].