Label-free in-situ real-time DNA hybridization kinetics detection employing microfiber-assisted Mach-Zehnder interferometer.

A label-free DNA biosensor based on microfiber-assisted Mach-Zehnder interferometer (MAMZI) for in-situ real-time DNA hybridization kinetics detection has been proposed and experimentally demonstrated. A microfiber of hundreds of microns in length is fabricated by tapering a segment of standard single-mode fiber (SMF) to construct the U-shaped microcavity between the lead-in and lead-out SMFs. Thanks to the mode field mismatching between the SMF and microfiber, the incident guided mode light would separate into two beams that respectively propagate in the air microcavity and the microfiber. Consequently, interference between different light modes would occur at the joint between the microfiber and the lead-out SMF. Experimental results indicate that owing to the participation of opening cavity modes in the modal interference process, the interferometric spectrum of our proposed microcavity sensor is highly sensitive to the variation of environmental refractive index (RI), especially for the RI range around 1.34 which is useful for most biological applications. The microfiber functionalization is achieved by stepwise modifying the microfiber with monolayer Poly-l-lysine (PLL) and single-stranded DNA (ssDNA) probes to produce the sensitive surface that could uniquely attach specific target ssDNAs. The fiber surface functionalization as well as DNA hybridization processes have been experimentally investigated for different target ssDNA solutions in real time. The interferometric transmission spectrum shows large wavelength shift for different biological phases, and a detection limit conservatively down to 0.0001pmol/μL has been acquired by employing the U-shaped microcavity of 176.88μm in length. Our proposed DNA biosensor possesses several advantages such as compact size, ease of fabrication, and strong response for DNA hybridization, which make it a promising candidate for potential applications in such rapidly expanding areas as medical diagnosis, cancer screenings, medicine examination and environmental engineering, etc.

[1]  Miao He,et al.  Ultrasensitive quantum dots-based DNA detection and hybridization kinetics analysis with evanescent wave biosensing platform. , 2011, Biosensors & bioelectronics.

[2]  Raj Mutharasan,et al.  Label-free detection of DNA hybridization using gold-coated tapered fiber optic biosensors (TFOBS) in a flow cell at 1310 nm and 1550 nm , 2008 .

[3]  Yinian Zhu,et al.  Long-period gratings in photonic crystal fiber as an optofluidic label-free biosensor. , 2011, Biosensors & bioelectronics.

[4]  B. Rahman,et al.  Optimization of a horizontal slot waveguide biosensor to detect DNA hybridization. , 2015, Applied optics.

[5]  D. Crothers,et al.  Interactions of heteroaromatic compounds with nucleic acids. 1. The influence of heteroatoms and polarizability on the base specificity of intercalating ligands. , 1975, European journal of biochemistry.

[6]  Yuze Sun,et al.  Sensitive optical biosensors for unlabeled targets: a review. , 2008, Analytica chimica acta.

[7]  Banshi D. Gupta,et al.  Fiber optic SPR sensor for the detection of 3-pyridinecarboxamide (vitamin B3) using molecularly imprinted hydrogel , 2013 .

[8]  M. Dagenais,et al.  Detecting hybridization of DNA by highly sensitive evanescent field etched core fiber Bragg grating sensors , 2005, IEEE Journal of Selected Topics in Quantum Electronics.

[9]  N. Dattagupta,et al.  Interactions of heteroaromatic compounds with nucleic acids. 2. Influence of substituents on the base and sequence specificity of intercalating ligands. , 1975, European journal of biochemistry.

[10]  Frank F Bier,et al.  Detection of activity of telomerase in tumor cells using fiber optical biosensors. , 2002, Biosensors & bioelectronics.

[11]  J. Lammertyn,et al.  Fiber optic SPR biosensing of DNA hybridization and DNA-protein interactions. , 2009, Biosensors & bioelectronics.

[12]  Stavros Pissadakis,et al.  Label-free DNA biosensor based on a peptide nucleic acid-functionalized microstructured optical fiber-Bragg grating , 2013, Journal of biomedical optics.

[13]  Qiang Liu,et al.  Micro-capillary-based evanescent field biosensor for sensitive, label-free DNA detection. , 2015, Optics express.

[14]  Chuji Wang,et al.  Fiber loop ringdown DNA and bacteria sensors. , 2011, Journal of biomedical optics.

[15]  D. Ikeda,et al.  Fabrication of core-shell structured nanoparticle layer substrate for excitation of localized surface plasmon resonance and its optical response for DNA in aqueous conditions. , 2010, Analytica chimica acta.

[16]  R Marchelli,et al.  Toward A Highly Specific DNA Biosensor: PNA-Modified Suspended-Core Photonic Crystal Fibers , 2010, IEEE Journal of Selected Topics in Quantum Electronics.

[17]  Hao Zhang,et al.  Ultrasensitive Refractive Index Sensor Based on Microfiber-Assisted U-Shape Cavity , 2013, IEEE Photonics Technology Letters.

[18]  B. Guan,et al.  In-situ DNA hybridization detection with a reflective microfiber grating biosensor. , 2014, Biosensors & bioelectronics.

[19]  J. Jensen,et al.  Photonic crystal fiber long-period gratings for biochemical sensing. , 2006, Optics express.

[20]  Frieder W. Scheller,et al.  Fibre-optic genosensor for specific determination of femtomolar DNA oligomers , 1997 .

[21]  Jeroen Lammertyn,et al.  Real-time monitoring of DNA hybridization and melting processes using a fiber optic sensor , 2012, Nanotechnology.