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Received: 2019-04-24

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Chen-lei Pang


Qing Yang


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Frontiers of Information Technology & Electronic Engineering  2020 Vol.21 No.8 P.1134-1149


Chip-based waveguides for high-sensitivity biosensing and super-resolution imaging

Author(s):  Chen-lei Pang, Xu Liu, Wei Chen, Qing Yang

Affiliation(s):  State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, Zhejiang University, Hangzhou 310027, China; more

Corresponding email(s):   qingyang@zju.edu.cn

Key Words:  Waveguide-based sensing, Waveguide-based imaging, Evanescent illumination, Frequency shifting and stitching

Chen-lei Pang, Xu Liu, Wei Chen, Qing Yang. Chip-based waveguides for high-sensitivity biosensing and super-resolution imaging[J]. Frontiers of Information Technology & Electronic Engineering, 2020, 21(8): 1134-1149.

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journal="Frontiers of Information Technology & Electronic Engineering",
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%T Chip-based waveguides for high-sensitivity biosensing and super-resolution imaging
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%A Xu Liu
%A Wei Chen
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%J Frontiers of Information Technology & Electronic Engineering
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%N 8
%P 1134-1149
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%D 2020
%I Zhejiang University Press & Springer
%DOI 10.1631/FITEE.1900211

T1 - Chip-based waveguides for high-sensitivity biosensing and super-resolution imaging
A1 - Chen-lei Pang
A1 - Xu Liu
A1 - Wei Chen
A1 - Qing Yang
J0 - Frontiers of Information Technology & Electronic Engineering
VL - 21
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SP - 1134
EP - 1149
%@ 2095-9184
Y1 - 2020
PB - Zhejiang University Press & Springer
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DOI - 10.1631/FITEE.1900211

In this review, we introduce some chip-based waveguide biosensing and imaging techniques, which significantly reduce the complexity of the entire system. These techniques use a well-confined evanescent field to interact with the surrounding materials and achieve high sensitivity sensing and high signal-to-noise ratio (SNR) super-resolution imaging. The fabrication process of these chips is simple and compatible with conventional semiconductor fabrication methods, allowing high-yield production. Combined with recently developed chip-based light sources, these techniques offer the possibility of biosensing and super-resolution imaging based on integrated circuits.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Abbe E, 1873. Beiträge zur theorie des mikroskops und der mikroskopischen wahrnehmung. Arch f Mikrosk Anat, 9(1):413-418 (in German).

[2]Agnarsson B, Ingthorsson S, Gudjonsson T, et al., 2009. Evanescent-wave fluorescence microscopy using symmetric planar waveguides. Opt Expr, 17(7):5075-5082.

[3]Agnarsson B, Lundgren A, Gunnarsson A, et al., 2015. Evanescent light-scattering microscopy for label-free interfacial imaging: from single sub-100 nm vesicles to live cells. ACS Nano, 9(12):11849-11862.

[4]Armani AM, Vahala KJ, 2006. Heavy water detection using ultra-high-Q microcavities. Opt Lett, 31(23):1896-1898.

[5]Axelrod D, 2001. Total internal reflection fluorescence microscopy in cell biology. Traffic, 2(11):764-774.

[6]Axelrod D, Thompson NL, Burghardt TP, 1983. Total internal reflection fluorescent microscopy. J Microsc-Oxford, 129(1):19-28.

[7]Bates M, Huang B, Dempsey GT, et al., 2007. Multicolor super-resolution imaging with photo-switchable fluorescent probes. Science, 317(5845):1749-1753.

[8]Betzig E, Trautman JK, 1992. Near-field optics: microscopy, spectroscopy, and surface modification beyond the diffraction limit. Science, 257(5067):189-195.

[9]Betzig E, Patterson GH, Sougrat R, et al., 2006. Imaging intracellular fluorescent proteins at nanometer resolution. Science, 313(5793):1642-1645.

[10]Brandenburg A, 1997. Differential refractometry by an integrated-optical Young interferometer. Sens Actuat B Chem, 39(1-3):266-271.

[11]Brandenburg A, Henninger R, 1994. Integrated optical Young interferometer. Appl Opt, 33(25):5941-5947.

[12]Chao CY, Fung W, Guo LJ, 2006. Polymer microring resonators for biochemical sensing applications. IEEE J Sel Top Quant, 12(1):134-142.

[13]Chung JW, Bernhardt R, Pyun JC, 2006. Additive assay of cancer marker CA 19-9 by SPR biosensor. Sens Actuat B Chem, 118(1-2):28-32.

[14]Coskun AF, Wong J, Khodadadi D, et al., 2013. A personalized food allergen testing platform on a cellphone. Lab Chip, 13(4):636-640.

[15]Cross GH, Ren YT, Freeman NJ, 1999. Young’s fringes from vertically integrated slab waveguides: applications to humidity sensing. J Appl Phys, 86(11):6483-6488.

[16]Cross GH, Reeves AA, Brand S, et al., 2003. A new quantitative optical biosensor for protein characterisation. Biosens Bioelectron, 19(4):383-390.

[17]Cush R, Cronin JM, Stewart WJ, et al., 1993. The resonant mirror: a novel optical biosensor for direct sensing of biomolecular interactions. Part I: principle of operation and associated instrumentation. Biosens Bioelectron, 8(7-8):347-354.

[18]Darafsheh A, Walsh GF, Dal Negro L, et al., 2012. Optical super-resolution by high-index liquid-immersed microspheres. Appl Phys Lett, 101(14):141128.

[19]de Vos K, Bartolozzi I, Schacht E, et al., 2007. Silicon-on- insulator microring resonator for sensitive and label-free biosensing. Opt Expr, 15(12):7610-7615.

[20]Diekmann R, Helle ØI, Øie CI, et al., 2017. Chip-based wide field-of-view nanoscopy. Nat Photon, 11(5):322-328.

[21]Fan XD, White IM, Shopova S, et al., 2008. Sensitive optical biosensors for unlabeled targets: a review. Anal Chim Acta, 620(1-2):8-26.

[22]Flueckiger J, Schmidt S, Donzella V, et al., 2016. Sub- wavelength grating for enhanced ring resonator biosensor. Opt Expr, 24(14):15672-15686.

[23]Goddard NJ, Pollard-Knight D, Maule CH, 1994. Real-time biomolecular interaction analysis using the resonant mirror sensor. Analyst, 119(4):583-588.

[24]Goddard NJ, Singh K, Hulme JP, et al., 2002. Internally- referenced resonant mirror devices for dispersion compensation in chemical sensing and biosensing applications. Sens Actuat A, 100(1):1-9.

[25]Graham CR, Leslie D, Squirrell DJ, 1992. Gene probe assays on a fibre-optic evanescent wave biosensor. Biosens Bioelectron, 7(7):487-493.

[26]Grandin HM, Städler B, Textor M, et al., 2006. Waveguide excitation fluorescence microscopy: a new tool for sensing and imaging the biointerface. Biosens Bioelectron, 21(8):1476-1482.

[27]Guner H, Ozgur E, Kokturk G, et al., 2019. A smartphone based surface plasmon resonance imaging (SPRi) platform for on-site biodetection. Sens Actuat B Chem, 239:571-577.

[28]Gustafsson MGL, 2005. Nonlinear structured-illumination microscopy: wide-field fluorescence imaging with theoretically unlimited resolution. Proc Natl Acad Sci USA, 102(37):13081-13086.

[29]Gustafsson MGL, Shao L, Carlton PM, et al., 2008. Three-dimensional resolution doubling in wide-field fluorescence microscopy by structured illumination. Biophys J, 94(12):4957-4970.

[30]Hanumegowda NM, White IM, Oveys H, et al., 2005. Label- free protease sensors based on optical microsphere resonators. Sens Lett, 3(4):315-319.

[31]Hao X, Kuang CF, Liu X, et al., 2011. Microsphere based microscope with optical super-resolution capability. Appl Phys Lett, 99(20):203102.

[32]Hao X, Liu X, Kuang CF, et al., 2013. Far-field super- resolution imaging using near-field illumination by micro-fiber. Appl Phys Lett, 102(1):013104.

[33]Hassanzadeh A, Nitsche M, Mittler S, et al., 2008. Waveguide evanescent field fluorescence microscopy: thin film fluorescence intensities and its application in cell biology. Appl Phys Lett, 92(23):233503.

[34]Hastings JT, Guo J, Keathley PD, et al., 2007. Optimal self-referenced sensing using long- and short-range surface plasmons. Opt Expr, 15(26):17661-17672.

[35]Hecht B, Sick B, Wild UP, et al., 2000. Scanning near-field optical microscopy with aperture probes: fundamentals and applications. J Chem Phys, 12(18):7761-7774.

[36]Heideman RG, Kooyman RPH, Greve J, et al., 1991. Simple interferometer for evanescent field refractive index sensing as a feasibility study for an immunosensor. Appl Opt, 30(12):1474-1479.

[37]Heideman RG, Kooyman RPH, Greve J, 1993. Performance of a highly sensitive optical waveguide Mach–Zehnder interferometer immunosensor. Sens Actuat B Chem, 10(3):209-217.

[38]Hess ST, Girirajan TPK, Mason MD, 2006. Ultra-high resolution imaging by fluorescence photoactivation localization microscopy. Biophys J, 91(11):4258-4272.

[39]Hoa XD, Kirk AG, Tabrizian M, 2007. Towards integrated and sensitive surface plasmon resonance biosensors: a review of recent progress. Biosens Bioelectron, 23(2):151-160.

[40]Homola J, Yee SS, Gauglitz G, 1999. Surface plasmon resonance sensors. Sens Actuat B Chem, 54(1-2):3-15.

[41]Horváth R, Lindvold LR, Larsen NB, 2002. Reverse- symmetry waveguides: theory and fabrication. Appl Phys B, 74(4-5):383-393.

[42]Horváth R, Pedersen HC, Skivesen N, et al., 2003. Optical waveguide sensor for on-line monitoring of bacteria. Opt Lett, 28(14):1233-1235.

[43]Horváth R, Pedersen HC, Skivesen N, et al., 2005. Monitoring of living cell attachment and spreading using reverse symmetry waveguide sensing. Appl Phys Lett, 86(7): 071101.

[44]Jiménez D, Bartolomé E, Moreno M, et al., 1996. An integrated silicon ARROW Mach–Zehnder interferometer for sensing applications. Opt Commun, 132(5-6):437-441.

[45]Kim J, Song KB, 2007. Recent progress of nano-technology with NSOM. Micron, 38(4):409-426.

[46]Kim J, Shin Y, Perera AP, et al., 2013. Label-free, PCR-free chip-based detection of telomerase activity in bladder cancer cells. Biosens Bioelectron, 45:152-157.

[47]Klar TA, Engel E, Hell SW, 2001. Breaking Abbe’s diffraction resolution limit in fluorescence microscopy with stimulated emission depletion beams of various shapes. Phys Rev E Stat Nonl Soft Matter Phys, 64(6):066613.

[48]Krioukov E, Greve J, Otto C, 2003. Performance of integrated optical microcavities for refractive index and fluorescence sensing. Sens Actuat B Chem, 90(1-3):58-67.

[49]Ksendzov A, Lin Y, 2005. Integrated optics ring-resonator sensors for protein detection. Opt Lett, 30(24):3344-3346.

[50]Lee D, Kim YD, Kim M, et al., 2017. Realization of wafer- scale hyperlens device for sub-diffractional biomolecular imaging. ACS Photon, 5(7):2549-2554.

[51]Liedberg B, Nylander C, Lunström I, 1983. Surface plasmon resonance for gas detection and biosensing. Sens Actuat, 4(2):299-304.

[52]Lillehoj PB, Huang MC, Truong N, et al., 2013. Rapid electrochemical detection on a mobile phone. Lab Chip, 13(15):2950-2955.

[53]Lin SY, Crozier KB, 2013. Trapping-assisted sensing of particles and proteins using on-chip optical microcavities. ACS Nano, 7(2):1720-1730.

[54]Lin VSY, Motesharei K, Dancil KPS, et al., 1997. A porous silicon-based optical interferometric biosensor. Science, 278(5339):840-843.

[55]Liu Q, Tu XG, Woo KK, et al., 2013. Highly sensitive Mach–Zehnder interferometer biosensor based on silicon nitride slot waveguide. Sens Actuat B Chem, 188:681-688.

[56]Liu XW, Kuang CF, Hao X, et al., 2017. Fluorescent nanowire ring illumination for wide-field far-field subdiffraction imaging. Phys Rev Lett, 118(7):076101.

[57]Liu ZW, Lee H, Xiong Y, et al., 2007. Far-field optical hyperlens magnifying sub-diffraction-limited objects. Science, 315(5819):1686.

[58]Ma DDD, Lee CS, Au FCK, et al., 2003. Small-diameter silicon nanowire surfaces. Science, 299(5614):1874-1877.

[59]Millan KM, Saraullo A, Mikkelsen SR, 1994. Voltammetric DNA biosensor for cystic fibrosis based on a modified carbon paste electrode. Anal Chem, 66(18):2943-2948.

[60]Moerner WE, 2007. New directions in single-molecule imaging and analysis. Proc Natl Acad Sci USA, 104(31):12596-12602.

[61]Nikitin PI, Grigorenko AN, Beloglazov AA, et al., 2000. Surface plasmon resonance interferometry for micro- array biosensing. Sens Actuat A, 85(1-3):189-193.

[62]Noto M, Khoshsima M, Keng D, et al., 2005. Molecular weight dependence of a whispering gallery mode biosensor. Appl Phys Lett, 87(22):223901.

[63]Pang CL, Liu XW, Zhuge MH, et al., 2017. High-contrast wide-field evanescent wave illuminated subdiffraction imaging. Opt Lett, 42(21):4569-4572.

[64]Pang CL, Li JX, Tang MW, et al., 2019. On-chip super- resolution imaging with fluorescent polymer films. Adv Funct Mat, 29(27):1900126.

[65]Prakash PA, Yogeswaran U, Chen SM, 2009. A review on direct electrochemistry of catalase for electrochemical sensors. Sensors, 9(3):1821-1844.

[66]Prieto F, Sepúlveda B, Calle A, et al., 2003. Integrated Mach–Zehnder interferometer based on ARROW structures for biosensor applications. Sens Actuat B Chem, 92(1-2):151-158.

[67]Ramachandran S, Cohen DA, Quist AP, et al., 2013. High performance, LED powered, waveguide based total internal reflection microscopy. Sci Rep, 3:2133.

[68]Rho J, Ye ZL, Xiong Y, et al., 2010. Spherical hyperlens for two-dimensional sub-diffractional imaging at visible frequencies. Nat Commun, 1:143.

[69]Roda A, Michelini E, Zangheri M, et al., 2016. Smartphone-based biosensors: a critical review and perspectives. Trends Anal Chem, 79:317-325.

[70]Rotenberg N, Kuipers L, 2014. Mapping nanoscale light fields. Nat Photon, 8(12):919-926.

[71]Schermelleh L, Heintzmann R, Leonhardt H, 2010. A guide to super-resolution fluorescence microscopy. J Cell Biol, 190(2):165-175.

[72]Schipper EF, Brugman AM, Dominguez C, et al., 1997. The realization of an integrated Mach–Zehnder waveguide immunosensor in silicon technology. Sens Actuat B Chem, 40(2-3):147-153.

[73]Schneider BH, Edwards JG, Hartman NF, 1997. Hartman interferometer: versatile integrated optic sensor for label- free, real-time quantification of nucleic acids, proteins, and pathogens. Clin Chem, 43(9):1757-1763.

[74]Schneider BH, Dickinson EL, Vach MD, et al., 2000. Highly sensitive optical chip immunoassays in human serum. Biosens Bioelectron, 15(1-2):13-22.

[75]Schweinsberg A, Hocdé S, Lepeshkin N, et al., 2007. An environmental sensor based on an integrated optical whispering gallery mode disk resonator. Sens Actuat B Chem, 123(2):727-732.

[76]Serpengüzel A, Arnold S, Griffel G, 1995. Excitation of resonances of microspheres on an optical fiber. Opt Lett, 20(7):654-656.

[77]Skivesen N, Horvath R, Pedersen HC, 2003. Multimode reverse-symmetry waveguide sensor for broad-range refractometry. Opt Lett, 28(24):2473-2475.

[78]Skivesen N, Horvath R, Pedersen HC, 2005. Optimization of metal-clad waveguide sensors. Sens Actuat B Chem, 106(2):668-676.

[79]Skivesen N, Horvath R, Thinggaard S, et al., 2007. Deep-probe metal-clad waveguide biosensors. Biosens Bioelectron, 22(7):1282-1288.

[80]Su H, Kallury KMR, Thompson M, et al., 1994. Interfacial nucleic acid hybridization studied by random primer 32P labeling and liquid-phase acoustic network analysis. Anal Chem, 66(6):769-777.

[81]Sun JB, Shalaev MI, Litchinitser NM, 2015. Experimental demonstration of a non-resonant hyperlens in the visible spectral range. Nat Commun, 6:7201.

[82]Sundram V, Nanda JS, Rajagopal K, et al., 1993. Domain truncation studies reveal that the streptokinase-plasmin activator complex utilizes long range protein-protein interactions with macromolecular substrate to maximize catalytic turnover. J Biol Chem, 278(33):30569-30577.

[83]Suter JD, White IM, Zhu HY, et al., 2007. Thermal characterization of liquid core optical ring resonator sensors. Appl Opt, 46(3):386-389.

[84]Taniguchi T, Hirowatari A, Ikeda T, et al., 2016. Detection of antibody-antigen reaction by silicon nitride slot-ring biosensors using protein G. Opt Commun, 365:16-23.

[85]Teraoka I, Arnold S, 2006. Theory of resonance shifts in TE and TM whispering gallery modes by nonradial perturbations for sensing applications. J Opt Soc Am B, 23(7): 1381-1389.

[86]Tian BZ, Cohen-Karni T, Qing Q, et al., 2010. Three- dimensional, flexible nanoscale field-effect transistors as localized bioprobes. Science, 329(5993):830-834.

[87]Tiefenthaler K, Lukosz W, 1989. Sensitivity of grating couplers as integrated-optical chemical sensors. J Opt Soc Am B, 6(2):209-220.

[88]Tong L, Gattass RR, Ashcom JB, et al., 2003. Subwavelength-diameter silica wires for low-loss optical wave guiding. Nature, 426(6968):816-819.

[89]Wang ZB, Guo W, Li L, et al., 2011. Optical virtual imaging at 50 nm lateral resolution with a white-light nanoscope. Nat Commun, 2:218.

[90]Watts HJ, Lowe CR, Pollard-Knight DV, 1994. Optical biosensor for monitoring microbial cells. Anal Chem, 66(15):2465-2470.

[91]Watts HJ, Yeung D, Partees H, 1995. Real-time detection and quantification of DNA hybridization by an optical biosensor. Anal Chem, 67(23):4283-4289.

[92]Weisser M, Tovar G, Mittler-Neher S, et al., 1999. Specific bio-recognition reactions observed with an integrated Mach–Zehnder interferometer. Biosens Bioelectron, 14(4):405-411.

[93]White IM, Fan XD, 2008. On the performance quantification of resonant refractive index sensors. Opt Expr, 16(2): 1020-1028.

[94]White IM, Gohring J, Fan XD, 2007. SERS-based detection in an optofluidic ring resonator platform. Opt Expr, 15(25):17433-17442.

[95]Willig KI, Rizzoli SO, Westphal V, et al., 2006. STED microscopy reveals that synaptotagmin remains clustered after synaptic vesicle exocytosis. Nature, 440(7086): 935-939.

[96]Yahiatène I, Hennig S, Müller M, et al., 2015. Entropy-based super-resolution imaging (ESI): from disorder to fine detail. ACS Photon, 2(8):1049-1056.

[97]Yalcin A, Popat KC, Aldridge JC, et al., 2006. Optical sensing of biomolecules using microring resonators. IEEE J Sel Top Quant, 12(1):148-155.

[98]Yang Q, Wang WH, Xu S, et al., 2011. Enhancing light emission of ZnO microwire-based diodes by piezo- phototronic effect. Nano Lett, 11(9):4012-4017.

[99]Ymeti A, Kanger JS, Greve J, et al., 2003. Realization of a multichannel integrated Young interferometer chemical sensor. Appl Opt, 42(28):5649-5660.

[100]Yu L, Shi ZZ, Fang C, et al., 2015. Disposable lateral flow-through strip for smartphone-camera to quantitatively detect alkaline phosphatase activity in milk. Biosens Bioelectron, 69:307-315.

[101]Zenhausern F, Martin Y, Wickramasinghe HK, 1995. Scanning interferometric apertureless microscopy: optical imaging at 10 angstrom resolution. Science, 269(5227): 1083-1085.

[102]Zhang JJ, Li GX, 2004. Third-generation biosensors based on the direct electron transfer of proteins. Anal Sci, 20(4):603-609.

[103]Zhang JL, Khan I, Zhang QW, et al., 2018. Lipopolysaccharides detection on a grating-coupled surface plasmon resonance smartphone biosensor. Biosens Bioelectron, 99:312-317.

[104]Zhu HY, Suter JD, White I, et al., 2006. Aptamer based microsphere biosensor for thrombin detection. Sensors, 6(8):785-795.

[105]Zourob M, Goddard NJ, 2005. Metal clad leaky waveguides for chemical and biosensing applications. Biosens Bioelectron, 20(9):1718-1727.

[106]Zourob M, Mohr S, Brown BJ, et al., 2003a. The development of a metal clad leaky waveguide sensor for the detection of particles. Sens Actuat B Chem, 90:296-307.

[107]Zourob M, Mohr S, Fielden PR, et al., 2003b. Small-volume refractive index and fluorescence sensor for micro total analytical system (μ-TAS) applications. Sens Actuat B Chem, 94:304-312.

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