# Sensor Micro and Nanoparticles for Microfluidic Application
## 2 Construction Principles of Sensor Particles
### Metal Particles for LSPR-Based Sensing  
Surface plasmons resonance (SPR) is a resonant oscillation of the incident light wave with the oscillations of charge density at metal and dielectric media interface [4]. For metallic rough surfaces, nanoparticles and sharp tips surface plasmons are thought to be confined in the nanoscale location by forming so-called localized surface plasmons resonance (LSPR), whose characteristic absorption band depends on species, size as well as shape of nanoparticles or metallic structures [33]. LSPR-based particle sensors are promising for the detection of changes in the refractive index (RI), which are caused by the analyte binding [1]. Non-labelling detection is the main advantage of the LSPR sensor compared with other techniques such as an isotope labelling or fluorescence [34]. Moreover, LSPR-based biosensors have unique properties allowing biomolecular analysis at real-time and detection of antigen-anti-body interaction or DNA hybridization even when the concentration of analyte is very low [35]. The binding of analytes on the surfaces of Au and Ag nanoparticles causes the changes in the surrounding environment's refractive index, which affects the spectroscopic properties (spectral shift or change in intensity) of the particle [35]. However, the LSPR signals can be affected by non-specific binding of molecules. Therefore, a sample for LSPR sensing should be pure and contain as little impurities as possible [34]. For practical purposes, colloidal gold or silver nanoparticles are embedded on the surface of solid material, where the laser light is usually used for excitation the LSPR. Then, optical setup collects the  
Figure 7: Schematic illustration of microcapsule functionalization with targeting antibodies: random antibody immobilization via EDC/sulfo-NHS reaction and optimized immobilization via protein A. Reprinted with permission from [32]. Copyright © 2017, American Chemical Society. light, which is scattered by the sample [36]. Due to the fact that the plasmonic effects can happen only near the metallic nanostructures, whose sizes are in nanometer range, LPSR-based sensing can be integrated in microfluidic systems [1]. Examples of particles used in microfluidic systems for LSPR-based sensing are given in Table 3.  
[PERSON] et al. [37] proposed a sensitive LSPR-based biosensor, which was applied for polypeptide detection. Using the proposed sensing system, the antigen-antibody interaction of bovine growth hormone was detected with the detection limit of 3.7 ng/mL as low as 185 pM; therefore, it was possible to use the biosensor for clinical applications. For LSPR sensing, gold nanoparticles were synthesized in a PDMS chip during an in-situ reaction between a gold precursor and polymer cross-linking agent. Despite the fact that the synthesis of the particles in microfluidic system was slower, formed AuNPs demonstrated 8.3 times better polydiversity of the size distribution. Four steps of the biosensing protocol are shown in Figure 8. Before performing the experiment, the gold nanoparticles were functionalized with 11-mercaptoethanolanoic acid. After attaching a linker, the activation of the carboxyl groups was carried out and after it, the antibody was attached to the surface of the functionalized gold nanoparticle. In the last step, the antigen was attached by introducing the solution of bovine growth hormone into the microfluidic channel. The immobilization of bovine growth hormone onto AuNPs resulted in increased refractive index and changes in the LSPR spectra. However, in order to improve and restore the proposed microfluidic biosensor for further measurement, the device can be integrated with a pump system and flow cells for channel rinsing purposes. Another microfluidic system for effective refractive index sensing was reported by [PERSON] et al. [38]. An integrated optofluidic system, which required a low sample volume and allowed a real-time monitoring of analyte, could be applied for non-invasive analysis and molecular diagnostics.