| Compared with the conventional laboratory,the microfluidics provides a practical advantage for the miniaturization of the reaction system,and is gradually being applied in the biomedical field.Surface Enhanced Raman Scattering?SERS?is an extremely powerful detection method,which not only yields information about the molecular structure of the analyte in the form of characteristic vibrational spectrum but also gives sensitivities approaching those in fluorescence spectroscopy.SERS measurements are easy to generate errors due to manual operation,however,a combined system consisting of microfluidics and SERS can transform processes of into automatic and highly repeatable detection,and change the detection process previously carried out on a large scale in the laboratory into a rapid detection in a small volume.Nonetheless,the conventional fabricating method of microfluidics requires expensive cleanrooms,and substantial human labors.Other fabricating methods of microfluidics without cleanrooms still need expensive and professional instruments,and with limited fabricating accuracy.Recently,microfluidics with flexible,transparent,stretchable and biocompatible soft tubule as microchannel have drawn much attention.In this paper,soft tubular microfluidics supported by 3D printed template was proposed,and it is combined with SERS to detect continuous fluid.First,in this paper,3D printed supporting templates were designed for planar and tridimensional microfluidics with curved channels based on the requirements of SERS detection and the characteristics of soft tubular microfluidics.By comparing the transparency,hardness,size and Raman background of soft tubules of 5 different materials,the Silicone tubule was selected and was assembled into soft tubular microfluidics together with the 3D printed supporting template and other accessories.Simulation results of solution mixing of two kinds of soft tubular microfluidics showed that they can mix solution efficiently.The effects of different flow rates on the SERS detection of planar and tridimensional microfluidics were demonstrated.The results showed that when the flow rate were 18?L/min and 16?L/min,the SERS spectra obtained from planar soft tubular microfluidics and tridimensional soft tubular microfluidics reached the maximum signal intensity and the smallest relative standard deviation?RSD?,and the peak area of characteristic peak of SERS spectra measured in the tridimensional microfluidics was about half that of the planar soft tubular microfluidics.Therefore,planar soft tubular microfluidics is more suitable for SERS detection of continuous fluid than tridimensional soft tubular microfluidics.Subsequently,three kinds of unit array planar soft tubular microfluidics with different channel shapes were designed on the basis of the previous part of the paper.The results of SERS detection showed that the optimal mixing unit number and aggregation unit number were 5 in U-shaped channel,and the characteristic peak area of measured SERS spectra of4-MBA at 1077 cm-1 and 1590 cm-1 were 34939±1886 and 60091±3118 with RSD of 5.40%and 5.19%,respectively.When SERS was detected in the semicircular channel soft tubular microfluidics,the optimal mixing unit number was 3 and the optimal aggregation unit number was 5,and the characteristic peak area of measured SERS spectra of 4-MBA at1077 cm-1 and 1590 cm-1 were 39113±1886 and 63603±3059 with RSD of 4.82%and4.81%,respectively.In the straight channel,when mixing unit number was 9 and aggregation unit number was 6,the characteristic peak area of measured SERS spectra of4-MBA at 1077 cm-1 and 1590 cm-1 were the maximum value of 25315±2530 and41117±1599,and their RSD values were 2.43%and 2.32%respectively.On the other hand,the variation trend of peak area of SERS spectra between different mixing unit number and aggregation unit number of semicircular channel soft tubular microfluidics was the most stable among different channel shapes.Finally,a continuous liquid SERS platform is proposed that combines SERS technique with soft tubular microfluidics for label-free detection of cell.Compared with common static solid and static liquid measurement,the continuous liquid SERS platform can achieve dynamical mixing of fluids,precise controls of the mixing time and continuous spectra collection.By characterizing the model molecules,the proposed dynamic liquid SERS platform have successfully achieved good stability and repeatability with 1.90%and4.98%RSD,respectively.Three cell lines including one normal breast cell lines?MCF-10A?and two breast cancer lines?MCF-7 and MDA-MB-231?were investigated.270 cell spectra were selected as the training set in the classification models based on K-Nearest Neighbor?K-NN?.A test set containing 180 cell spectra successfully classified three cell lines with sensitivities of>83.3%,specificities of>91.6%and 94.4%accuracy.In this paper,soft tubular microfluidics supported by 3D printed template was successfully demonstrated.SERS measurements and analysis were carried out on soft tubular microfluidics with different dimensions and different channel shapes.And the application of soft tubular microfluidics supported by 3D printed template were actively explored in SERS detection of continuous fluid.The continuous fluid SERS platform can achieve higher signal intensity,better repeatability,with no preparatory work and can obtain abundant spectra in a short time,which will be a powerful detection tool in cell research,clinical diagnosis,and food safety. |
PDF Full Text Request