超灵敏检测中信号扰动分析及应用
Analysis and Application of Signal Fluctuation in Ultra-Sensitive Detection
DOI: 10.12677/AAC.2022.122015, PDF,    国家自然科学基金支持
作者: 胡玉林:南通大学化学化工学院,江苏 南通;华 宇, 刘 扬, 吴增强*:南通大学公共卫生学院,江苏 南通
关键词: 超灵敏检测信号扰动噪音分析纳米限域效应时域信号频域信号Ultra-Sensitive Detection Signal Fluctuation Noise Analysis Nano-Confined Effect Time Domain Signal Frequency Domain Signal
摘要: 随着相关技术的发展,分析检测方法正在逐步向亚皮摩尔的检测限逼近的同时也面临一系列挑战。其中最大的挑战是目标分子或离子检测浓度的降低使相应的检测信号也降低,甚至有可能低于环境的背景噪音,以致于实际的检测信号被掩盖。为解决这一问题,关键在于提高检测技术的信噪比。因此,这篇综述主要探讨了超灵敏检测的进展和面临的挑战以及如何提高信噪比的方法。其中包括利用纳米孔和纳米通道的限域效应来放大目标检测物的信号的方法,但是仍然存在如何降低背景噪音的问题,因为限域的空间对信号放大是没有选择性的。另一种思路是利用噪音扰动分析,对检测信号进行时域或频域的相关处理,将其从背景噪音中分离,从而获得检测物的具体信息。最后,本综述结合这两个方面解决思路对超灵敏检测的未来发展作出了展望。
Abstract: The ultra-sensitive determination methods have been approaching to Sub-Picomolar detection limit as well as confronting a series of challenges, where the greatest challenge we have to overcome is that lower level of detected signal resulting from lower concentration of target molecules is normally masked by background noise. Improving signal to noise ratio (S/N ratio) of detection method is a critical solution to address this concern. Therefore, in this review, we summarized the recent advances and challenges in ultra-sensitive detection and discussed methods to improve S/N ratio. Applying nano-confined effect of nanopore and nanochannel to amplify detected signal of target molecules is an efficient strategy. Meanwhile, since background noise is also magnified, reducing background noise is still a limiting factor in developing ultra-sensitive detection. Another strategy is to separate detected signals that are masked by background signal by applying noise analysis with the help of numerical method. Finally, we provide a brief discussion about future trend in developing ultra-sensitive detection.
文章引用:胡玉林, 华宇, 刘扬, 吴增强. 超灵敏检测中信号扰动分析及应用[J]. 分析化学进展, 2022, 12(2): 111-124. https://doi.org/10.12677/AAC.2022.122015

参考文献

[1] Gubala, V., Harris, L.F., Ricco, A.J., Tan, M.X. and Williams, D.E. (2011) Point of Care Diagnostics: Status and Future. Analytical Chemistry, 84, 487-515.
[Google Scholar] [CrossRef] [PubMed]
[2] Kelley, S.O. (2016) What Are Clinically Relevant Levels of Cellular and Biomolecular Analytes? ACS Sensors, 2, 193-197.
[Google Scholar] [CrossRef] [PubMed]
[3] Wu, Y.F., Tilley, R.D. and Gooding, J.J. (2018) Challenges and Solutions in Developing Ultrasensitive Biosensors. Journal of the American Chemical Society, 141, 1162-1170.
[Google Scholar] [CrossRef] [PubMed]
[4] Singh, P.S. and Lemay, S.G. (2016) Stochastic Processes in Electrochemistry. Analytical Chemistry, 88, 5017-5027.
[Google Scholar] [CrossRef] [PubMed]
[5] Bizzarri, A.R. and Cannistraro, S. (2013) 1/f(alpha) Noise in the Dynamic Force Spectroscopy Curves Signals the Occurrence of Biorecognition. Physical Review Letters, 110, Article ID: 048104.
[Google Scholar] [CrossRef
[6] Bizzarri, A.R. and Cannistraro, S. (2014) Antigen-Antibody Biorecognition Events as Discriminated by Noise Analysis of Force Spectroscopy Curves. Nanotechnology, 25, Article ID: 335102.
[Google Scholar] [CrossRef] [PubMed]
[7] Bizzarri, A.R. (2016) Energy Landscape Investigation by Wavelet Transform Analysis of Atomic Force Spectroscopy Data in a Biorecognition Experiment. Journal of Biological Physics, 42, 167-176.
[Google Scholar] [CrossRef] [PubMed]
[8] Bizzarri, A.R., Vegh, A.G., Varo, G. and Cannistraro, S. (2019) Interaction Force Fluctuations in Antigen-Antibody Biorecognition Studied by Atomic Force Spectroscopy. ACS Omega, 4, 3627-3634.
[Google Scholar] [CrossRef
[9] Kasas, S., Malovichko, A., Villalba, M.I., Vela, M.E., Yantorno, O. and Willaert, R.G. (2021) Nanomotion Detection-Based Rapid Antibiotic Susceptibility Testing. Antibiotics, 10, Article No. 287.
[Google Scholar] [CrossRef] [PubMed]
[10] Kasas, S., Ruggeri, F.S., Benadiba, C., Maillard, C., Stupar, P., Tournu, H., Dietler, G. and Longo, G. (2015) Detecting Nanoscale Vibrations as Signature of Life. Proceedings of the National Academy of Sciences of the United States of America, 112, 378-381.
[Google Scholar] [CrossRef] [PubMed]
[11] Willaert, R.G., Vanden Boer, P., Malovichko, A., Alioscha-Perez, M., Radotic, K., Bartolic, D., Kalauzi, A., Villalba, M.I., Sanglard, D., Dietler, G., Sahli, H. and Kasas, S. (2020) Single Yeast Cell Nanomotions Correlate with Cellular Activity. Science Advances, 6, 1-8.
[Google Scholar] [CrossRef] [PubMed]
[12] Shabi, O., Natan, S., Kolel, A., Mukherjee, A., Tchaicheeyan, O., Wolfenson, H., Kiryati, N. and Lesman, A. (2020) Motion Magnification Analysis of Microscopy Videos of Biological Cells. PLoS ONE, 15, Article ID: e0240127.
[Google Scholar] [CrossRef] [PubMed]
[13] Kwon, T., Gunasekaran, S. and Eom, K. (2019) Atomic Force Microscopy-Based Cancer Diagnosis by Detecting Cancer-specific Biomolecules and Cells. Biochimica et Biophysica Acta—Reviews on Cancer, 1871, 367-378.
[Google Scholar] [CrossRef] [PubMed]
[14] Ruggeri, F.S., Sneideris, T., Vendruscolo, M. and Knowles, T.P.J. (2019) Atomic Force Microscopy for Single Molecule Characterisation of Protein Aggregation. Archives of Biochemistry and Biophysics, 664, 134-148.
[Google Scholar] [CrossRef] [PubMed]
[15] Valotteau, C., Sumbul, F. and Rico, F. (2019) High-Speed Force Spectroscopy: Microsecond Force Measurements Using Ultrashort Cantilevers. Biophysical Reviews, 11, 689-699.
[Google Scholar] [CrossRef] [PubMed]
[16] Lissandrello, C., Inci, F., Francom, M., Paul, M.R., Demirci, U. and Ekinci, K.L. (2014) Nanomechanical Motion of Escherichia coli Adhered to a Surface. Applied Physics Letters, 105, Article ID: 113701.
[Google Scholar] [CrossRef] [PubMed]
[17] Yu, H., Siewny, M.G.W., Edwards, D.T., Sanders, A.W. and Perkins, T.T. (2017) Hidden Dynamics in the Unfolding of Individual Bacteriorhodopsin Proteins. Science, 355, 945-950.
[Google Scholar] [CrossRef] [PubMed]
[18] Beaussart, A. and El-Kirat-Chatel, S. (2019) Microbial Adhesion and Ultrastructure from the Single-Molecule to the Single-Cell Levels by Atomic Force Microscopy. The Cell Surface, 5, Article ID: 100031.
[Google Scholar] [CrossRef] [PubMed]
[19] Newton, R., Delguste, M., Koehler, M., Dumitru, A.C., Laskowski, P.R., Mueller, D.J. and Alsteens, D. (2017) Combining Confocal and Atomic Force Microscopy to Quantify Single-Virus Binding to Mammalian Cell Surfaces. Nature Protocols, 12, 2275-2292.
[Google Scholar] [CrossRef] [PubMed]
[20] Ghosh, H. and Roy Chaudhuri, C. (2013) Ultrasensitive Food Toxin Biosensor Using Frequency Based Signals of Silicon Oxide Nanoporous Structure. Applied Physics Letters, 102, Article ID: 243701.
[Google Scholar] [CrossRef
[21] Ghosh, H. and Roy Chaudhuri, C. (2015) Noise Spectroscopy as An Efficient Tool for Impedance Based Sub-Femtomolar Toxin Detection in Complex Mixture Using Nanoporous Silicon Oxide. Biosensors and Bioelectronics, 67, 757-762.
[Google Scholar] [CrossRef] [PubMed]
[22] Rivnay, J., Leleux, P., Hama, A., Ramuz, M., Huerta, M., Malliaras, G.G. and Owens, R.M. (2015) Using White Noise to Gate Organic Transistors for Dynamic Monitoring of Cultured Cell Layers. Scientific Reports, 5, Article ID: 11613.
[Google Scholar] [CrossRef] [PubMed]
[23] Kulkarni, G.S. and Zhong, Z. (2012) Detection Beyond the Debye Screening Length in a High-Frequency Nanoelectronic Biosensor. Nano Letters, 12, 719-723.
[Google Scholar] [CrossRef] [PubMed]
[24] Laborde, C., Pittino, F., Verhoeven, H.A., Lemay, S.G., Selmi, L., Jongsma, M.A. and Widdershoven, F.P. (2015) Real-Time Imaging of Microparticles and Living Cells with CMOS Nanocapacitor Arrays. Nature Nanotechnology, 10, 791-795.
[Google Scholar] [CrossRef] [PubMed]
[25] Cossettini, A., Laborde, C., Brandalise, D., Widdershoven, F., Lemay, S.G. and Selmi, L. (2021) Space and Frequency Dependence of Nanocapacitor Array Sensors Response to Microparticles in Electrolyte. IEEE Sensors Journal, 21, 4696-4704.
[Google Scholar] [CrossRef
[26] Zheng, G., Gao, X.P.A. and Lieber, C.M. (2010) Frequency Domain Detection of Biomolecules Using Silicon Nanowire Biosensors. Nano Letters, 10, 3179-3183.
[Google Scholar] [CrossRef] [PubMed]
[27] Setiadi, A., Fujii, H., Kasai, S., Yamashita, K.-I., Ogawa, T., Ikuta, T., Kanai, Y., Matsumoto, K., Kuwahara, Y. and Akai-Kasaya, M. (2017) Room-Temperature Discrete-Charge-Fluctuation Dynamics of a Single Molecule Adsorbed on a Carbon Nanotube. Nanoscale, 9, Article ID: 10674-10683.
[Google Scholar] [CrossRef
[28] Vasudevan, S. and Ghosh, A.W. (2014) Using Room Temperature Current Noise to Characterize Single Molecular Spectra. ACS Nano, 8, 2111-2117.
[Google Scholar] [CrossRef] [PubMed]
[29] Mathwig, K., Mampallil, D., Kang, S. and Lemay, S.G. (2012) Electrical Cross-Correlation Spectroscopy: Measuring Picoliter-per-Minute Flows in Nanochannels. Physical Review Letters, 109, Article ID: 118302.
[Google Scholar] [CrossRef
[30] Zevenbergen, M.A.G., Singh, P.S., Goluch, E.D., Wolfrum, B.L. and Lemay, S.G. (2009) Electrochemical Correlation Spectroscopy in Nanofluidic Cavities. Analytical Chemistry, 81, 8203-8212.
[Google Scholar] [CrossRef] [PubMed]
[31] Zevenbergen, M.A.G., Singh, P.S., Goluch, E.D., Wolfrum, B.L. and Lemay, S.G. (2011) Stochastic Sensing of Single Molecules in a Nanofluidic Electrochemical Device. Nano Letters, 11, 2881-2886.
[Google Scholar] [CrossRef] [PubMed]
[32] Kaetelhoen, E., Krause, K.J., Singh, P.S., Lemay, S.G. and Wolfrum, B. (2013) Noise Characteristics of Nanoscaled Redox-Cycling Sensors: Investigations Based on Random Walks. Journal of the American Chemical Society, 135, 8874-8881.
[Google Scholar] [CrossRef] [PubMed]
[33] Singh, P.S., Chan, H.-S.M., Kang, S. and Lemay, S.G. (2011) Stochastic Amperometric Fluctuations as a Probe for Dynamic Adsorption in Nanofluidic Electrochemical Systems. Journal of the American Chemical Society, 133, Article ID: 18289-18295.
[Google Scholar] [CrossRef] [PubMed]
[34] Hoogerheide, D.P., Garaj, S. and Golovchenko, J.A. (2009) Probing Surface Charge Fluctuations with Solid-State Nanopores. Physical Review Letters, 102, Article ID: 256804.
[Google Scholar] [CrossRef
[35] Powell, M.R., Sa, N., Davenport, M., Healy, K., Vassiouk, I., Letant, S.E., Baker, L.A. and Siwy, Z.S. (2011) Noise Properties of Rectifying Nanopores.The Journal of Physical Chemistry C, 115, 8775-8783.
[Google Scholar] [CrossRef
[36] Bezrukov, S.M. and Kasianowicz, J.J. (1993) Current Noise Reveals Protonation Kinetics and Number of Ionizable Sites in an Open Protein Ion Channel. Physical Review Letters, 70, 2352-2355.
[Google Scholar] [CrossRef
[37] Nekolla, S., Andersen, C. and Benz, R. (1994) Noise Analysis of Ion Current through the Open and the Sugar-induced Closed State of the LamB Channel of Escherichia Coli Outer Membrane: Evaluation of the Sugar Binding Kinetics to the Channel Interior. Biophysical Journal, 66, 1388-1397.
[Google Scholar] [CrossRef
[38] Nestorovich, E.M., Danelon, C., Winterhalter, M. and Bezrukov, S.M. (2002) Designed to Penetrate: Time-resolved Interaction of Single Antibiotic Molecules with Bacterial Pores. Proceedings of the National Academy of Sciences of the United States of America, 99, 9789-9794.
[Google Scholar] [CrossRef] [PubMed]
[39] Queralt-Martin, M., Lidon Lopez, M. and Alcaraz, A. (2015) Excess White Noise to Probe Transport Mechanisms in a Membrane Channel. Physical Review E, 91, Article ID: 062704.
[Google Scholar] [CrossRef
[40] Zorkot, M., Golestanian, R. and Bonthuis, D.J. (2016) The Power Spectrum of Ionic Nanopore Currents: The Role of Ion Correlations. Nano Letters, 16, 2205-2212.
[Google Scholar] [CrossRef] [PubMed]
[41] Zorkot, M., Golestanian, R. and Bonthuis, D.J. (2016) Current Fluctuations in Nanopores: The Effects of Electrostatic and Hydrodynamic Interactions. The European Physical Journal Special Topics, 225, 1583-1594.
[Google Scholar] [CrossRef
[42] Fragasso, A., Pud, S. and Dekker, C. (2019) 1/f Noise in Solid-State Nanopores Is Governed by Access and Surface Regions. Nanotechnology, 30, Article ID: 395202.
[Google Scholar] [CrossRef] [PubMed]
[43] Gravelle, S., Netz, R.R. and Bocquet, L. (2019) Adsorption Kinetics in Open Nanopores as a Source of Low-Frequency Noise. Nano Letters, 19, 7265-7272.
[Google Scholar] [CrossRef] [PubMed]
[44] Rigo, E., Dong, Z., Park, J.H., Kennedy, E., Hokmabadi, M., Almonte-Garcia, L., Ding, L., Aluru, N. and Timp, G. (2019) Measurements of the Size and Correlations Between Ions Using an Electrolytic Point Contact. Nature Communications, 10, Article No. 2382.
[Google Scholar] [CrossRef] [PubMed]
[45] Yusko, E.C., Johnson, J.M., Majd, S., Prangkio, P., Rollings, R.C., Li, J., Yang, J. and Mayer, M. (2011) Controlling Protein Translocation through Nanopores with Bio-Inspired Fluid Walls. Nature Nanotechnology, 6, 253-260.
[Google Scholar] [CrossRef] [PubMed]
[46] Yusko, E.C., Bruhn, B.R., Eggenberger, O.M., Houghtaling, J., Rollings, R.C., Walsh, N.C., Nandivada, S., Pindrus, M., Hall, A.R., Sept, D., Li, J., Kalonia, D.S. and Mayer, M. (2017) Real-Time Shape Approximation and Fingerprinting of Single Proteins Using a Nanopore. Nature Nanotechnology, 12, 360-367.
[Google Scholar] [CrossRef] [PubMed]
[47] Fologea, D., Ledden, B., McNabb, D.S. and Li, J. (2007) Electrical Characterization of Protein Molecules by a Solid-State Nanopore. Applied Physics Letters, 91, Article ID: 053901.
[Google Scholar] [CrossRef] [PubMed]
[48] Robertson, J.W.F., Rodrigues, C.G., Stanford, V.M., Rubinson, K.A., Krasilnikov, O.V. and Kasianowicz, J.J. (2007) Single-Molecule Mass Spectrometry in Solution Using a Solitary Nanopore. Proceedings of the National Academy of Sciences of the United States of America, 104, 8207-8211.
[Google Scholar] [CrossRef] [PubMed]
[49] Raillon, C., Cousin, P., Traversi, F., Garcia-Cordero, E., Hernandez, N. and Radenovic, A. (2012) Nanopore Detection of Single Molecule RNAP-DNA Transcription Complex. Nano Letters, 12, 1157-1164.
[Google Scholar] [CrossRef] [PubMed]
[50] Soni, G.V. and Dekker, C. (2012) Detection of Nucleosomal Substructures Using Solid-State Nanopores. Nano Letters, 12, 3180-3186.
[Google Scholar] [CrossRef] [PubMed]
[51] Di Fiori, N., Squires, A., Bar, D.; Gilboa, T., Moustakas, T.D. and Meller, A. (2013) Optoelectronic Control of Surface Charge and Translocation Dynamics in Solid-State Nanopores. Nature Nanotechnology, 8, 946-951.
[Google Scholar] [CrossRef] [PubMed]
[52] Yusko, E.C., Prangkio, P., Sept, D., Rollings, R.C., Li, J. and Mayer, M. Single-Particle Characterization of a Beta Oligomers in Solution. ACS Nano, 6, 5909-5919.
[CrossRef] [PubMed]
[53] Houghtaling, J., Ying, C., Eggenberger, O.M., Fennouri, A., Nandivada, S., Acharjee, M., Li, J., Hall, A.R. and Mayer, M. (2019) Estimation of Shape, Volume, and Dipole Moment of Individual Proteins Freely Transiting a Synthetic Nanopore. ACS Nano, 13, 5231-5242.
[Google Scholar] [CrossRef] [PubMed]
[54] German, S.R., Hurd, T.S., White, H.S. and Mega, T.L. (2015) Sizing Individual Au Nanoparticles in Solution with Sub-Nanometer Resolution. ACS Nano, 9, 7186-7194.
[Google Scholar] [CrossRef] [PubMed]
[55] Boskovic, F., Zhu, J., Chen, K. and Keyser, U.F. (2019) Monitoring G-Quadruplex Formation with DNA Carriers and Solid-State Nanopores. Nano Letters, 19, 7996-8001.
[Google Scholar] [CrossRef] [PubMed]
[56] Li, X., Lee, K.H., Shorkey, S., Chen, J. and Chen, M. (2020) Different Anomeric Sugar Bound States of Maltose Binding Protein Resolved by a Cytolysin a Nanopore Tweezer. ACS Nano, 14, 1727-1737.
[Google Scholar] [CrossRef] [PubMed]
[57] Liu, S.C., Li, M.X., Li, M.Y., Wang, Y.Q., Ying, Y.L., Wan, Y.J. and Long, Y.T. (2018) Measuring a Frequency Spectrum for Single-Molecule Interactions with a Confined Nanopore. Faraday Discussions, 210, 87-99.
[Google Scholar] [CrossRef
[58] Zhu, H., Ma, G., Wan, Z., Wang, H. and Tao, N. (2020) Detection of Molecules and Charges with a Bright Field Optical Microscope. Analytical Chemistry, 92, 5904-5909.
[Google Scholar] [CrossRef] [PubMed]
[59] Ma, G., Shan, X., Wang, S. and Tao, N. (2019) Quantifying Ligand-Protein Binding Kinetics with Self-Assembled Nano-Oscillators. Analytical Chemistry, 91, Article ID: 14149-14156.
[Google Scholar] [CrossRef] [PubMed]
[60] Wang, H., Tang, Z., Wang, Y., Ma, G. and Tao, N. (2019) Probing Single Molecule Binding and Free Energy Profile with Plasmonic Imaging of Nanoparticles. Journal of the American Chemical Society, 141, Article ID: 16071-16078.
[Google Scholar] [CrossRef] [PubMed]
[61] Guerra, L.F., Muir, T.W. and Yang, H. (2019) Single-Particle Dynamic Light Scattering: Shapes of Individual Nanoparticles. Nano Letters, 19, 5530-5536.
[Google Scholar] [CrossRef] [PubMed]
[62] Gutierrez-Portocarrero, S., Sauer, K., Karunathilake, N., Subedi, P. and Alpuche-Aviles, M.A. (2020) Digital Processing for Single Nanoparticle Electrochemical Transient Measurements. Analytical Chemistry, 92, 8704-8714.
[Google Scholar] [CrossRef] [PubMed]
[63] Gu, Z., Ying, Y.L., Cao, C., He, P. and Long, Y.T. (2019) Accurate Data Process for Nanopore Analysis. Analytical Chemistry, 87, 907-913.
[Google Scholar] [CrossRef] [PubMed]
[64] Liu, X., Zeng, Q., Liu, C. and Wang, L. (2020) A Fourier Transform-Induced Data Process for Label-Free Selective Nanopore Analysis Under Sinusoidal Voltage Excitations. Analytical Chemistry, 92, Article ID: 11635-11643.
[Google Scholar] [CrossRef] [PubMed]
[65] Cho, S.Y., Lee, Y., Lee, S., Kang, H., Kim, J., Choi, J., Ryu, J., Joo, H., Jung, H.T. and Kim, J. (2020) Finding Hidden Signals in Chemical Sensors Using Deep Learning. Analytical Chemistry, 92, 6529-6537.
[Google Scholar] [CrossRef] [PubMed]
[66] Wei, Z.X., Ying, Y.L., Li, M.Y., Yang, J., Zhou, J.L., Wang, H.F., Yang, B.Y. and Long, Y.T. (2019) Learning Shapelets for Improving Single-Molecule Nanopore Sensing. Analytical Chemistry, 91, Article ID: 10033-10039.
[Google Scholar] [CrossRef] [PubMed]
[67] Arima, A., Harlisa, I.H., Yoshida, T., Tsutsui, M., Tanaka, M., Yokota, K., Tonomura, W., Yasuda, J., Taniguchi, M., Washio, T., Okochi, M. and Kawai, T. (2018) Identifying Single Viruses Using Biorecognition Solid-State Nanopores. Journal of the American Chemical Society, 140, Article ID: 16834-16841.
[Google Scholar] [CrossRef] [PubMed]
[68] Arima, A., Tsutsui, M., Harlisa, I.H., Yoshida, T., Tanaka, M., Yokota, K., Tonomura, W., Taniguchi, M., Okochi, M., Washio, T. and Kawai, T. (2018) Selective Detections of Single-viruses Using Solid-state Nanopores. Scientific Reports, 8, Article No. 16305.
[Google Scholar] [CrossRef] [PubMed]
[69] Arima, A., Tsutsui, M., Yoshida, T., Tatematsu, K., Yamazaki, T., Yokota, K., Kuroda, S.I., Washio, T., Baba, Y. and Kawai, T. (2020) Digital Pathology Platform for Respiratory Tract Infection Diagnosis via Multiplex Single-Particle Detections. ACS Sensors, 5, 3398-3403.
[Google Scholar] [CrossRef] [PubMed]
[70] Alessio, F., Sonja, S. and Cees, D. (2020) Comparing Current Noise in Biological and Solid-State Nanopores. ACS Nano, 14, 1338-1349.
[Google Scholar] [CrossRef] [PubMed]