Inkjet Printing And Microfluidics Based Droplets Generation And Applications

Droplet is an important technical tool for biological and chemical applications.However,the generation of droplets remains to be a huge challenge from the technical perspective.Therefore,it is necessary to develop rapid,convenient and high throughput methods for droplet generation.Microfluidics is the mainstream platform for droplet generation,and has been employed in a variety of applications.However,the complex manufacturing process,high processing cost and harsh requirements on the surrounding environment limit its further applications.In recent years,inkjet printing technology is adopted by more and more researchers due to the rapid development in its simplicity,flexibility and cost efficiency.In this paper,we employed both inkjet printing technology and microfluidic technology to generate microdroplets,and applied the generated microdroplets for material synthesis and ultrasensitive nucleic acid detection.The main contents are as follows:(1)Inkjet printing based ultra-small MnO2 nanosheets synthesis for glutathione sensing.(2)Inkjet printing based droplet digital loop-mediated isothermal amplification for HPV16 detection.(3)Microfluidics based droplet digital PCR for circulating tumor DNA detection.The main contents of the dissertation are as follows:(1)Manganese dioxide(MnO2)with small size is competent in sensing applications,but its synthesis generally adopts templates or in complex ways.Inkjet printing technique with excellent performance offers a versatile tool due to its stability,flexibility,and economy.Herein,an inkj et printing method was developed for rapid synthesis of ultra-small MnO2 nanosheets.The feasibility of inkjet printing method for MnO2 nanosheets synthesis was demonstrated with great performance in small size and facile mode.Additionally,the limit of detection(LOD)of ultra-small MnO2 nanosheets in glutathione(GSH)sensing is 0.26 ?M,which was about 40%more sensitive than that of the typical MnO2 nanosheets.By virtue of the inkjet printing approach,the ultra-small MnO2 nanosheets was obtained in a short time without complicated fabricating process.It can be foreseen that the proposed inkjet printing approach would facilitate the application prospects of ultra-small MnO2 nanosheets in diverse fields.Such a facile approach may open new avenues for synthesis of ultra-small or ultrafine nanomaterials.(2)Increased adoption of HPV testing is expected in light of a growing global awareness of women's health and the recent launch of cervical cancer vaccines.Developing rapid and inexpensive diagnostic tools toward HPV detection has been pushed forward by the advancements on technical aspects.However,rarely attention has been paid to molecular detection methodology with the combination of inkjet printing with microfluidics.Herein,we developed an approach that integrated inkjet printing and microfluidics as the enabling technology to realize digital LAMP for HPV 16 detection in a low-cost and practical format.Inkjet printing technique,a simple method for the generation of monodisperse droplets in controllable volumes from picoliter to nanoliter.The microfluidic chip serves as droplets collection chamber for LAMP assays.We believe this simple and low-cost droplet digital LAMP approach offers great opportunity for rapid quantification of other HPV subtypes,and can be extended for other pathogens such as bacteria.(3)The advancement on microfluidics has been leveraged toward the development of state-of-the-art platforms for molecular diagnostics.Digital polymerase chain reaction(dPCR)is currently one of the most sensitive method for quantitative determination of nucleic acids.Herein,we combined microfluidics with droplet digital polymerase chain reaction(ddPCR)on an all-in-one intergrated chip that allows for monodisperse droplet generation,amplification,and absolute quantification.The intergrated microfluidic chip utilized flow-focusing design that can rapidly produce-30 ?m droplets with high throughput.Furthermore,on-chip thermal cycling was carried out without applying commercial apparatus to the device.The integrated microfluidic chip was successfully applied to quantify circulating tumor DNA(ctDNA),KRAS G13D,and can be further extended to any other cancer biomarkers.The all-in-one integrated microfluidic chip is affordable and easy to use,and can be used as a promising diagnostic tool.We envision that this integrated microfluidic chip could be further extended to point-of-care-test(POCT)related applications,especially in resource-limited areas.