*2.4. Others*

Neurotransmitters are important for information transmission in the nervous system. Catecholamines are a kind of biological amine neurotransmitters consisting of amino and catechol in structure. The sensitive and accurate detection of catecholamines is significant for brain function research and neurological diseases monitoring. Dopamine is one of catecholamine class that plays an important role in human physiology. Tang et al. [84] developed an aptamer-induced Au@Ag nanorod dimer self-assembly method to detect the dopamine ultrasensitively with a LOD of 0.006 pM. Besides the detection methods based on aptamers and antibodies, Dumont et al. [85] developed a salt-induced colloid pre-aggregation strategy to overcome the protein corona stabilization for analysis of serum samples. Moreover, the analysis of multiple catecholamines in the complex was also achieved by SERS detection. Cao et al. [86] utilized an Au-Fe Raman label for the rapid detection of dopamine, norepinephrine or epinephrine in complex serum. Moody et al. [87] developed a SERS sensor for rapid analysis of seven neurotransmitters using AuNPs and AuNPs at multiple excitation wavelengths.

### **3. Application on the Detection of Plant Original Biomolecules**

Compared to the application of SERS on the detection of animal original biomolecules, there were far fewer reports about the plant originated biomolecules, which are mainly concentrated in foods or medicinal plants, such as antioxidants, anthocyanins, Chinese herbal medicinal ingredients and so on. SERS also has been applied to the molecular fingerprint identification of plant while very few applications of SERS have been explored in the basis physiological study of model plants [88,89].

### *3.1. Lipids and Antioxidant*

Lipids are the main food components, which are critical for nutrition concerns [90,91]. Study on their oxidative status can help the storage and process industry. Plants are known for their antioxidative effects due to their secondary metabolites, which can be used as food additives to avoid lipid oxidation. Unsaturated fatty acids also are important for the quality and bioactivity of lipids [92,93]. For the SERS detection of lipids and antioxidants, nanomaterials such as AgNPs and AuNPs were mainly used to fabricate the SERS-active substrate using the nanofabrication methods of *e*-beam lithography [94], electroless plating [95], and so on. Interaction of targets and nanomaterials was investigated in detail to improve the sensitivity of SERS detection.

SERS have favorable potential to offer exact information of the chemical constitution of the lipid and its oxidation state. Li et al. [89] investigated the SERS assay using silver (Ag) dendrites to enhance SERS signal of detecting canola oil and alpha-tocopherol, the oxidation process of canola oil was also investigated. SERS showed better sensitivity than general Raman or ultraviolet (UV) methods in monitoring the transformation of lipid structure when oxidated. Tomato represents a major horticultural crop in human diet. Carotenoids, a kind of antioxidant rich in tomatoes, are important for plant physiology and mammalian organisms [96]. Radu et al. studied the differences of two kinds of carotenoids in tomato extracts using an *e*-beam lithography SERS-active substrate. A model sample which was a mixture of two kinds of carotenoids was processed and analyzed. Two data processing methods were used, and the result agreed with the conventional analysis methods [94].

Chan et al. [97] described the preparation of nanoarrays with AgNPs used as SERS substrates. The nanoparticle-based platform offered application prospects in SERS analysis of beta-carotene, and the detection limit was <0.63 ppm. Hsueh et al. [95] created a facile designed 3D substrate for SERS detection of beta-carotene. The SERS devices had high-density, uniformly distributed hotspots of gold (Au) multibranches, which were electroless plated with a nanoporous polymer as a template. The sensitivity, stability and reproducibility were investigated. The new approach provided new substrate fabricating method for the analysis of analytes with an enhancement factor of 108.

SERS was also used to detect butylated hydroxyanisole (BHA), generally used in foods or oil products to avoid oxidation [98]. Direct determination of BHA in several edible and essential oils without any sample treatment was realized by using SERS with a low-cost homemade silver substrate. The detailed conditions of experiment, characterics of every kind of oil, and the traits of substrate were showed and discussed [99]. Interaction of targets and nanomaterials is crucial for the improvement of the LOD of a SERS based detection. Studies on SERS detection of catechin showed that the ratio of catechin to AgNPs and NaCl was important for the data quality. Raman signal was detectable at 10−<sup>18</sup> M level at the optimized ratio. Raman detection of catechin with high sensitivity and reproducibility was achieved due to the obvious enhancement of Raman signal [100]. Aguilar-Hernandez et al. [88] systematically evaluated SERS measurements of several examples of antioxidants compounds derived from various plants.
