Research On Design And Fabrication Methods For POCT Polymer Microfluidic Chips

Point-of-care tesing technology is able to make untrained people obtain the in-site testing results accurately and efficiently,which has a wide application in the fields of early diagnosis of serious disease,personalized healthcare,environmental monitoring and health quarantine.The core task of POCT technology is to design and fabricate portable,inexpensive,multi-function integrated and autonomous-running devices according to different testing demands.Microfluidic chip has the advantages of minimization,integration and portability,which is the prospective device to achieve the purpose of POCT.Polymer materials are the important materials for fabricating microfluidic chips,which are relatively easy-processing and have a good bio-compatibility.These advantages of polymers make the POCT microfluidic chip capable of mass manufacturing,resulting in its development from experiments to commercializations.However,nowadays,there are still some issues for POCT polymer micro fluidic chips:(1)The structures of the micro fluidic self-driven manipulation unit are complex and lack theoretical model;(2)The stability and performance of the chips are severely compromised because of the low accuracy and efficiency of the fabricating process;(3)In the multi-function integrated microfluidic chips,it is challenging to realize the continuous,differential and self-driven control of the microfluid;(4)POCT optical detection system has a low integration level and the coupling process of the optical components is complicated.In order to address the above issues,some researches were carried out as follows.(1)In terms of the issues that the microfluidic manipution units lack theoretical model,based on the free surface energy theory the capillary barrier model was put forward to control the flow behavior of the microfluid.The criterion that microfluid can stop at the edge of the capillary barrier was demonstrated.The self-driven flowing mechanism was presented and the influence factors of the self-driven velocity in the rectangular microchannels were studied as well.Based on the capillary barrier model,the comlike time-control unit as well as the wavelike buffering unit was designed,which can control the flowing time precisely and generate a uniform flowing behavior.Through the finite element method,the effect of size parameters of the two units on the performance of the fluid control was presented,which provided the basis for the design of POCT microfluidic chips.Finially,a multi-function integrated POCT microfluidic chip was designed,which integrated the wavelike buffering unit,sample introduction unit,comlike time-control unit,testing unit and waste sample collection unit.(2)In order to address the inaccuracy and inefficiency bonding issue for the POCT polymer microfluidic chip,a laser-bulge based ultrasonic bonding(LBUB)method was demonstrated,which included the "mask overlapping" technique,the optimized bulge dimension and layout.Based on the theoretical analysis,finite element method and experiment validations,the mechanism of bulge generation and the relationship between the laser parameters and bulge dimensions were illustrated.The ultrasonic bonding parameters were optimized using the substrates fabricated by hot embossing process.Using the bulge for ultrasonic bonding,the melted bulge can flow into the laser-ablated groove,which can avoid the molten polymer remaining between the bonding interfaces.The results show that the LBUB method has the advantages of high bonding accuracy(the microchannel loss is about 0.5μm,taking 0.6%of the microchannel dimention),high bonding efficiency(the bonding time is about 10s)and high bonding strength(the bonding strength is about 1.92MPa).(3)In order to realize the differential flow manipulation and the region-selective antibody absorption,a controllable gradient UV Irradiation(CGUI)method was presented.In this method,the quartz plates with different thickness of Cu film were used to control the UV irradiation.A bespoke modification device was designed and fabricated.The relationship between the Cu film and the UV irridation energy was demonstrated.By applying the CGUI method,the liquid flow tests and the antibody adsorption experiments were conducted.The results show that subsequent to 5min CGUI treatment,the contact angle for different parts of the PMMA surface can be varied from 45.50 to 77.40 continuously,achieving the differential flow manipulation.The antibody adsorption strength and the wettability of the PMMA material exhibit an inverse relationship,providing the potential for region-selective antibody absorption.(4)Based on a self-aligned on-chip focusing(SOF)lenses,a smarphone-based POCT immunofluorescence assay system was presented.The optical geometry models of single/compound lenses were built.Based on the models,the relationships between the optical performance and the materials as well as the dimensions of the SOF lenses were studied.Based on the SOF lenses,a portable assay device was designed and fabricated.A smartphone app for the assay process was developed.Applying the palm-sized system(length×width×height=105mm×85mm×40mm),by toughing a few icons of the smartphone,the funcition of fluorescence image capturing,analyzing,memorizing and history consulting can be realized.The results show that the proposed SOF lenses can enhance about 4-fold fluorescence intensity.The lower detection limit of FITC solutions is about 0.06pg/ml and the detection limit of 83 pg/ml and 97pg/ml for cTnI are attained in buffer and spiked human serum,respectively,which is within the range of clinically acceptable concentrations(10～100 pg/ml).