Research And Development Of Paper-based Analysis Technology And Device

People's health is an important symbol of national prosperity and national prosperity.Since the Central Committee and the State Council issued and implemented the "healthy China 2030"outline plan in October 25,2016,comrade Xi Jinping has put forward the strategy of "healthy China" in the nineteen major reports.China has been improving the clinical diagnosis and medical service system,strengthening the establishment of a healthy environment,ensuring food and drug safety and shaping self independence and self-discipline,and preventing drugs.In the field of people's livelihood,we will continue to improve the system,deepen the reform,and develop relevant research,so as to provide a full range of full cycle health services for the people.Simple,fast and reliable on-site screening,detection and analysis technology and device can not only become an important means of supervision and evidence collection,but also provide early warning for major emergency public health events.At present,the detection and analysis technologies used in the above fields include:infrared spectroscopy,gas chromatography-mass spectrometry,high performance liquid chromatography-mass spectrometry,etc.Although these analytical methods have high sensitivity and extremely low detection limit,they need to rely on large and expensive laboratory level instruments,and the sample pretreatment operation is complex,the overall detection and analysis time is long,and the detection cost is high.Compared with the above characteristics of laboratory level analysis technology,paper-based analysis technology with its low cost,simple operation,short detection time,portable and other advantages is more suitable for the establishment of analysis and detection outside the laboratory environment,and can even provide low-cost clinical diagnosis solutions in the areas of lack of medical resources.However,the paper-based analysis technology still faces some problems,such as unclear analysis principle,low sample concentration,difficult sensitivity to meet the detection needs,few special analysis technologies for special analytes,and poor portability of on-site screening detection and analysis platform devices,which restrict its application.After a large number of related literature research,this paper takes paper-based analysis technology as the breakthrough point,in order to solve the above problems in the technology as the goal,the following work has been carried out:paper-based FASS(Field Amplified Sample Stacking)field amplified sample stacking enrichment principle of multi physical field simulation research;research on a new method of highly sensitive paper-based SERS(Surface-Enhanced Raman Scattering)detection based on electrokinetic stacking technology;The development of high sensitive EXPAR(exponential amplification reaction)and paper-based nucleic acid enrichment analysis method based on unilateral thio template and the portable fluorescence immunopaper chromatography detection and analysis device based on smart phone.The innovative achievements are as follows:(1)A multi-physical simulation model of paper based field amplification and electrodynamic stacking FASS with multiple coupled physical fields(electric potential field,electrical conductivity field,fluid field and concentration field)was established.Finite element analysis and solution were conducted to study the principle of paper-based electrodynamic stacking,and the simulation results were verified through practical experiments.(2)A highly sensitive method for rapid and efficient preparation of paper-based SERS by electrokinetic stacking was proposed.The method and device for preparation of paper-based SERS nano gold substrate by field amplified electrokinetic stacking(FASS)technology were proposed for the first time.Rhodamine 6G and crystal violet were analyzed.Compared with other methods,this method has the advantages of simple operation,low cost and greatly reduced preparation time,limit of detection(LOD)increased by 3 orders of magnitude.(3)The simulation system of density functional theory was constructed to calculate the bases before and after unilateral thio.The results show that the ability of oligonucleotides after thio to obtain electrons is reduced and the chemical stability is enhanced.This weakens the ability to form hydrogen bonds with complementary deoxynucleotides,and finally reduces the possibility of binding complementarity,which theoretically verifies the feasibility of using unilateral thio template to improve the LOD of EXPAR.(4)A highly sensitive EXPAR analysis method using a unilateral thiogen template was developed.Sulfur atoms were used for the first time to replace phosphorus atoms at the base deoxidization condensation at the 5 'end of the template,which inhibited non-specific amplification to improve EXPAR sensitivity.Under the same conditions,EXPAR LOD of unilateral thiocarbon template was optimized from 10-12 mol/L to 10-15 mol/L(5)A smart phone field screening drug detection device based on time-resolved fluorescence immunochromatography paper-based analysis technology was developed.The device adopted the modular design of 3D printing technology,and the developed special APP was used to process and analyze the fluorescent image of the paper strip.The device was used to carry out the methamphetamine standard and the hair detection method for drug users.The LOD of this device for methamphetamine is as low as 3.34×10-9 mol/L,and the linear range is 3.91×10-9 mol/L to 1×10-6 mol/L.The stability(CV=2.35%)can meet the requirements of on-site screening.The whole detection process will be completed within 10 minutes.At the same time,a smart phone-based on-site pesticide residue detection device was developed,which can be adapted to the transformed immunochromatographic detection strip,and can complete the detection of organophosphorus pesticides within 10 minutes.