Hollow-Core Optical Fiber Optofluidic DNA Sensor Based on Whispering Gallery Mode
Objective The specific detection of DNA sequences plays a vital role in disease diagnosis,drug development,environmental protection,and other fields.Common DNA detection methods include electrochemical detection,semiconductor detection,and optical detection.Although the electrochemical detection method features high precision and strong practicability,it has the disadvantages of high cost and complicated detection processes.Semiconductor detection methods can detect reaction changes in real time,but the experimental operation is difficult and has strict requirements for experimental volume.Optical fiber biosensors based on the whispering gallery mode(WGM)effect have been extensively studied due to their small size,high detection accuracy,and fast response.For the measurement requirements of in-situ DNA sensing,we propose an optical fiber optofluidic sensor based on hollow-core fiber WGM.Methods The proposed sensor is prepared by coupling a tapered optical fiber and a hollow-core fiber.The sensor mainly employs the evanescent field generated by the tapered optical fiber to excite the hollow-core fiber resonant cavity to generate WGM for detection.From the perspective of the sensor composition,the diameter of the tapered fiber,the thickness of the resonant cavity,and the coupling distance between the tapered fiber and the resonant cavity will all influence the experimental detection results.Meanwhile,we explore the proposed DNA sensor from both simulation and experiment aspects.By conducting simulation analysis via Comsol software,we first obtain how the above three factors affect the experimental results.The experiment is completed under the guidance of the simulation.Additionally,we adopt the hollow-core fiber as the resonant cavity and the internal air hole of the hollow-core fiber as the microfluidic channel.In the experiment,the silanization method is utilized to immobilize probe DNA(pDNA)on the surface of the resonant cavity for subsequent detection of complementary DNA(cDNA).Results and Discussions The simulation experiments can help draw the following three conclusions.The smaller diameter of the tapered zone of the tapered fiber leads to a stronger evanescent field generated by the tapered fiber.When the thickness of the resonant cavity continues to decrease,the higher electric field in the resonant cavity brings stronger generated WGM.Under the constant diameter of the tapered fiber and thickness of the resonant cavity,the WGM phenomenon will occur when the coupling spacing between the tapered fiber and the resonant cavity is reduced to a certain distance.The experimental results show that reducing the thickness of the resonant cavity can improve the sensor sensitivity.When the thickness of the resonator is 4.5 μm,the refractive index sensitivity is 141 nm/RIU.The simulation results indicate that reducing the thickness of the resonant cavity can increase the sensor sensitivity.Meanwhile,we leverage hydrofluoric acid to corrode the thickness of the resonant cavity.When the thickness of the resonator is 2 μm,the refractive index sensitivity can reach 206 nm/RIU,1.4 times higher than that of the resonator with a thickness of 4.5 μm.The thickness of the resonant cavity less than 2 μm is not suitable for practical experiments.The thickness of the hollow-core fiber during the preparation process is not completely uniform.When the thickness of the resonant cavity corroded by hydrofluoric acid is less than 2 μm,it is easy to corrode the thinner parts of the resonant cavity.Additionally,to achieve the introduction of the liquid to be measured,we employ a pump to transport the liquid,which will generate pressure on the resonant cavity and cause the microfluidic channel to rupture under the thin thickness.The resonant cavity with a thickness of 2 μm meets the requirements for detecting local refractive index changes that occur on the optical fiber surface due to the hybridization of DNA molecules.The specific detection of complementary DNA can be achieved by immobilizing the pDNA inside the microfluidic channel of the hollow-core fiber resonator.We prepare cDNA solutions with five concentrations of 10 nmol/L,50 nmol/L,100 nmol/L,200 nmol/L,and 1 μmol/L for concentration gradient detection.When the concentration is 10-100 nmol/L,since the amount of pDNA on the inner surface of the resonant cavity is large enough,linear changes occur with the increasing cDNA concentration.When the concentration of cDNA is 200 nmol/L,the remaining pDNA cannot completely bind to cDNA and therefore cannot change linearly.When the concentration of cDNA continues to rise,there is no excess pDNA on the fiber surface,the sensor reaches a saturated state,and the spectrum no longer shifts.Therefore,the proposed sensor has a linear detection range of 10-100 nmol/L,a sensitivity of 0.56 pm/(nmol/L),and a linearity of 0.994,and it has sound stability and selectivity.Conclusions In this paper,we proposed and exhibited a high-sensitivity optical fiber DNA sensor.The WGM fiber probe was fabricated by embedding a corroded hollow core fiber into the tapered fiber structure,and the WGMs could be excited through the efficient coupling between the thin hollow core fiber and the tapered fiber.WGMs in the resonator are excited by evanescent coupling using the tapered fiber with 1.2 μm waist diameter.The combination of proposed DNA and complementary DNA will increase the effective refractive index of the microtubule change,and result in transmission spectrum change finally.Studies of the DNA response sensitivity,stability,and selectivity dependence of the proposed sensor are carried out.The sensitivity achieved in our experiments was 0.56 pm/(nmol/L)in the DNA range from 10 nmol/L to 100 nmol/L.Our DNA sensor based on the WGM effect has the advantage of label-free detection,laying the foundation for the applications of in-situ DNA detection in medical diagnosis and prognosis.
medical opticsoptofluidic optical fiber sensorwhispering gallery modein-situ DNA sensing
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