Researches On Fabrication And Application Of Multifunctional Microfluidic Array Chips

Recently,microfluidic technology has drawn much research efforts to solve major problems for assays,separations coupled to detection device,bioanalyses,and synthesis of organic or inorganic compounds for possessing the advantages of high throughput,little sample consumption,and good consistency,which greatly improve the researches.However,with the rapidly increasing demands for high-throughput,automated,integrated microfluidic system,traditional microfluidic chips are more and more difficult to meet the demands.Chips with more functions,higher throughput and more systematic are needed.Based on these facts,here we proposed several applications about microfluidic chips in analytical chemistry.1.Fabrication and application of liquid gradient in two-dimensional matrixIn order to conduct high throughput drug screening on chip,we expand traditional one dimensional chips into two-dimensional matrix and designed two microfluidic platforms.Firstly,two multi layered structure are fabricated for cell and bacterium culture,then two types of 2D liquid gradient are utilized to deliver drugs in different concentrations to well cultured cells or bacterium.The first liquid gradient combined a premixer gradient generator and diffusion based gradient generator.The traditional one dimension(1D)gradient suffers badly to the finite number of available data points due to the limitation of chip size and pressure.As comparison,2D matrix has the advantages of higher gradient content under the same pressure condition.Moreover;the combination of two gradient generators gives us the opportunity to overcome their respective defects,the resultant gradient possesses constant and tunable concentration without introducing shear force to cells.For drug screening applications,the concentration gradient of model medicine Dox(Doxorubicin)was generated on this platform for HL-60 cells treatment.It is observed that cell viability related intimately with the Dox concentration.Dox and Que(Quercetin)were then employed simultaneously to generate an overlapping gradient,and its effect on HL-60 cells was further explored.The second liquid gradient utilized PDMS and paper-based chips,to build a semi-open droplets array.A premixer gradient generator is integrated to give the droplets array different concentrations.We utilize this structure to deliver drugs to a gel array with coli bacillus.The gel array runs through the chip to allow drug delivery from both top and bottom hence gradient is expanded into two dimensional.Both 2D gradient chips are characterized theoretically and experimentally,and applied to high throughput drug screening assays on chip.These two microfluidic platforms may provide a promising tool for future high throughput drug screening.2.Fabrication and application of versatile microfluidic droplets array chipsWe proposed a microfluidic device with a novel way for liquid dispensation without complicated control system or extra forces.We built a regional hydrophilic chip via plasma treated PDMS with nano patterns.Just making the chip surface in contact with the reagent,a droplets array was obtained automatically,which made the chip an ideal platform for diagnostic testing.Droplets from picoliters to nanoliters were obtained.By combining this chip with a Christmas Tree gradient generator,a droplets array in gradient was achieved,showing its superiority in integration.A rapid biosensing chip for carcinoma embryonic antigen(CEA)was developed via labeled magnetic beads(MBs).This chip meets the requirement of user-friendly and may be developed as a new tool for the point-of-care analysis.Based on this fast sampling method,we applied these droplets to in situ synthesize AuNPs,as well as an evaporation control system for long time droplets reactions.Upon equipping nanoparticles with a designed hairpin DNA,this chip was able to detect specific DNA sequences.3.A Nature Mimicking Microfluidic Lung Model for Passive Smoking AnalysisWe built a novel microfluidic lung-on-a-chip that mimics the respiration process down to the single alveolar level.The "alveolar" units are composed of thin PDMS layer on supporting structures that can be dynamically driven by external pressure.The movement was well tuned both by its amplitude and rhythm following the natural process of human respiration.By integrating the alveolar units into arrays and assembling them to gas channels,an artificial lung was successfully constructed.Upon equipping this system with a droplet array on the alveolar array surface,we were able to get information on relationship between individual respiratory movement and contents in smoke.Here,with sidestream cigarette smoking(SSS)as an example,analysis of its accumulation for target molecules during passive smoking is taken.Clarification of relationships between nicotine in cigarette and the passive breathing time,distances away from smokers are realized for the first time.Moreover,simultaneous collection and multiplex analysis of different species in SSS are realized on chip.