## 4 Conclusions  
In this work we reviewed the latest results when applying the SERS method for isolation, identification, and analysis of exosome-like vesicles. The literature search has shown that these SERS analysis methods can be divided into two: label-free and immunolabeling approaches. While both strategies suffer from some limitations such as spectral overlapping, complex data analysis in the label-free approach, and the difficulties of sensor functionalization with receptor molecules for immunolabeling assay, they were successfully applied for in vitro SERS identification of exosomes isolated from the corresponding cell lines or blood samples from patients. In particular, the label-free SERS regime along with a trained multivariate analysis has shown potential in discriminating between the exosomes isolated from healthy and cancerous cell lines. The possibility to collect the biochemical composition of intact exosomes is another valuable advantage of label-free SERS detection. At the same time, the immunolabeling approach has demonstrated higher specificity in detecting exosomes compared to data obtained in the label-free regime. In addition, antibody functionalized SERS nanotags demonstrated multiplexing capabilities, which are extremely important to probe exosomes in complex media without a purification step or in a sample with different populations of exosomes. However, despite recent success in the identification of exosome-like vesicles by the SERS method, several problems need to be solved to enable highly effective and rapid detection of tumor-derived exosomes in real patient samples. One of the most difficult problems in exosome detection in clinical applications is to specifically detect tumor-derived exosomes in the samples containing exosomes that are isolated from normal cells. The heterogeneity of disease-specific exosomes and exosomal cargo that eventually influence the accuracy of the SERS analysis is another considerable challenge. The possible solutions to overcome the biological and technical challenges can be: (i) The right selection of the established exosomal markers; (ii) measuring a sufficiently large population of exosomes to differentiate between common exosomal peaks and specific ones; (iii) the development of normative exosomal pools of healthy heterogeneous populations of exosomes; (iv) controlling the spatial localization of SERS sensors on the exosome samples to obtain enhancements from components of interest. The combination of optical and spectroscopic components, and novel assay design into an integrated system for selective isolation of various exosome subpopulations in heterogeneous samples can substantially enhance the potential of the SERS method for use in practical applications. The integrated optofluidic chip designed for multiwavelength fluorescence and Raman spectroscopy is a good example to be used in the analysis of liquid samples [109]. An important step towards the fabrication of an on-chip SERS platform combining the sensing area, filters, and spectrometer on a single chip was demonstrated in prior research [110]. Furthermore, the reduction of both the size and cost of the Raman spectrometers will enable the development of ultrasensitive, user-friendly, and low-cost miniature integrated systems for on-site SERS diagnosis.