Research Of The Bio-chips Integrated With LSPR Sensing And Microfluidic System

Along with the continuous development of life sciences, biomedical detectionand biochemical analysis have getting more and more attention of the researchers,and the microfluidic systems have also gradually become a research hotspot. Themain work of this paper is fabricating a high sensitivity biochip system, whichintegrated the traveling-wave piezoelectric micropump and Localized SurfacePlasmon Resonance (LSPR) sensing device onto the glass substrate, to achieve theminiaturized and inexpensive test, on the basis of the study of LSPR extinctionproperties of the gold nanoparticles. The novel microchannel structure of thetraveling-wave piezoelectric micropump was designed to improve the micropumpefficiency in the fabrication of the micropump. In order to provide the theoreticalanalysis of the gold nanoparticles at the LSPR sensing area, the extinction propertiesof the gold nanoparticles array was simulated by Discrete Dipole Approximation(DDA) method to obtain the sensitivity influence of the array density. Furthermore,the molecular reaction procedure on the nanoparticles’ surface was tested by theextinction properties in the visible region. The research of this paper developed anintegrated LSPR biochip system applied to the biomedical test with the advantages ofminiaturezation, low cost and high sensitivity. The main work includes:1. Theoretical simulation of the traveling-wave piezoelectric micropumps. Theamplitude theoretical model of piezoelectric bimorphs and the formationmechanism of microchannels were analyzed in detail, while the piezoelectricbimorphs were selected as the micropump actuators; the piezoelectric bimorphwas modeled by Finite Element Analysis software ANSYS, and the influence ofthe important factors toward the amplitude of the piezoelectric bimorph weresimulated to optimize the design parameters; meanwhile, the inside displacementresponse of the PDMS microchannel was simulated when the piezoelectricbimorphs generated different displacement on the microchannel.2. Design and fabrication of the traveling-wave piezoelectric micropump. The micropump substrate and microchannel mold were fabricated with PMMA bymicromachining technology, and the microchannel was formed by liquid polymermaterial PDMS using injection molding process; the traveling-wave piezoelectricmicropump would be done while the microchannel was bonded onto the substateby thermal bonding process, and the piezoelectric bimorphs array was fixed onthe pump area of the microchannel; the pump area configuration of themicrochannel was designed as a saw-tooth stucture of multi-stage diffuser, whichwas improved the maximum flow rate and the maximum back pressure of themicropump at the lower voltage, the average flow rate and back pressurerespectively reached33.36μL/min and1.13kPa; with the same testing conditions,these two parameters of straight microchannel were respectively24.88μL/minand0.64kPa, which are much smaller than those of saw-tooth microchannel.3. The simulation of the extinction properties of different nanoparticles andnanoparticles arrays. The LSPR extinction of nanoparticles with differentmaterial, shape, size and array structure were simulated by Discrete DipoleApproximation (DDA) and Finite-Difference Time-Domain (FDTD) method; theextinction properties of spherical nanoparticles arrays with different spacing weresimulated by DDA method, and the simulation results indicate that the extinctionwavelength and intensity were increasing with the decreasing nanoparticlesspacing, but the refractive index (RI) sensitivity remained a constant essentiallywhen the nanoparticles spacing was large enough. Therefore, the local unevendistribution of the nanoparticles array would not change its RI sensitivity as thespacing between nanoparticles is large enough.4. The testing of the LSPR biosensor chip. The spherical gold nanoparticles wassynthetized by sodium citrate reduction method, and fixed on the silanized glasssubstrate by self-assembly technology, forming a monolayer of gold nanoparticlesarray; the extinction properties of gold nanoparticles arrays in different mediumwas tested, and the influence to the RI sensitivity of the biosensor chip withdifferent array spacing was researched.5. The fabrication of integrated LSPR biosensing system. The traveling-wavepiezoelectric micropump, which applied to deliver the sample to the sensing area, was integrated on the LSPR biosensor chip by ultraviolet bonding process, andthe optical fiber was introduced into the LSPR sensing area; thus, the LSPRsensor and the off-chip optical detection equipment were connected together toforming the integrated LSPR biosensing system.6. The application of Biological immune measurement. The mercapto acid,crosslinking agent (EDC/NHS) and goat anti-human IgG were successivelytransported to the LSPR sensing membrane of gold nanoparticles array bytraveling-wave piezoelectric micropump to modify the probe molecules, and theLSPR extinction spectrum of each step of the modifying reaction procedure wastest by spectrophotometer to obtain the biosensor chip with higher sensitivity.