**2. Label-free techniques**

In previous works, the real-time monitoring of cell secretion was achieved by label-free techniques such as plasmonic sensors, or label-required techniques such as fluorescence microscopy. The principles for all these methods are demonstrated in **Figure 1**. The representative works are summarized as shown in **Table 1**.

#### **2.1 Plasmonic sensors**

Plasmonic sensors have received tremendous attention owing to the label-free process, high sensitivity and fast response [36–38]. Plasmonic sensors generate surface plasmons and evanescence field that is sensitive to the changes of refractive index on sensing interfaces [39, 40]. By functionalization of the sensing interfaces, the change of refractive index upon specific binding of target molecules can be recognized. The plasmonic sensing could be implemented on varying materials, geometries and structures, such as flat metal films (surface plasmon resonance)

*Advanced Biosensing towards Real-Time Imaging of Protein Secretion from Single Cells DOI: http://dx.doi.org/10.5772/intechopen.94248*

**Figure 1.** *Demonstration of methodology towards the real-time imaging of protein secretion from single cells.*

[41, 42], nanoparticles (localized surface plasmon resonance) [43, 44] and nanoholes (extraordinary optical transmission) [45, 46]. These differences result in diverse applications and sensor performances.



#### *Advanced Biosensing towards Real-Time Imaging of Protein Secretion from Single Cells DOI: http://dx.doi.org/10.5772/intechopen.94248*



#### **Table 1.**

*Summery for detection methodology of real-time monitoring of cell secretion.*
