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Research Article

Relay-type sensing mode: A strategy to push the limit on nanomechanical sensor sensitivity based on the magneto lever

Depeng Rao§Tianhao Yan§Zihan QiaoYu WangYongpei PengHan TuShangquan Wu( )Qingchuan Zhang( )
CAS Key Laboratory of Mechanical Behavior and Design of Material, Department of Modern Mechanics, University of Science and Technology of China, Hefei 230027, China

§ Depeng Rao and Tianhao Yan contributed equally to this work.

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Graphical Abstract

Herein, we developed a novel ultrasensitive relay-type sensing mode. A nanomechanical sensor based on the magneto-lever was used as an example, and an improved detection limit up to five orders of magnitude was achieved, as compared with the conventional aptasensor. More importantly, under sufficiently high lever, even single-molecule resolution can theoretically be achieved.

Abstract

Ultrasensitive molecular detection and quantization are crucial for many applications including clinical diagnostics, functional proteomics, and drug discovery; however, conventional biochemical sensors cannot satisfy the stringent requirements, and this has resulted in a long-standing dilemma regarding sensitivity improvement. To this end, we have developed an ultrasensitive relay-type nanomechanical sensor based on a magneto lever. By establishing the link between very weak molecular interaction and five orders of magnitude larger magnetic force, analytes at ultratrace level can produce a clearly observable mechanical response. Initially, proof-of-concept studies showed an improved detection limit up to five orders of magnitude when employing the magneto lever, as compared with direct detection using probe alone. In this study, we subsequently demonstrated that the relay-type sensing mode was universal in application ranging from micromolecule to macromolecule detection, which can be easily extended to detect enzymes, DNA, proteins, cells, viruses, bacteria, chemicals, etc. Importantly, we found that, sensitivity was no longer subject to probe affinity when the magneto lever was sufficiently high, theoretically, even reaching single-molecule resolution.

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References

[1]

Liu, W. P.; Pan, S. T.; Zhang, H. X.; Tang, Z. F.; Liang, J.; Wang, Y. Y.; Zhang, M. L.; Hu, X. D.; Pang, W.; Duan, X. X. A universal biomolecular concentrator to enhance biomolecular surface binding based on acoustic NEMS resonator. ACS Cent. Sci. 2018, 4, 899–908.

[2]

Mellman, I.; Warren, G. The road taken: Past and future foundations of membrane traffic. Cell 2000, 100, 99–112.

[3]

Guo, K. Y.; Wustoni, S.; Koklu, A.; Díaz-Galicia, E.; Moser, M.; Hama, A.; Alqahtani, A. A.; Ahmad, A. N.; Alhamlan, F. S.; Shuaib, M. et al. Rapid single-molecule detection of COVID-19 and MERS antigens via nanobody-functionalized organic electrochemical transistors. Nat. Biomed. Eng. 2021, 5, 666–677.

[4]

Foley, E. D. B.; Kushwah, M. S.; Young, G.; Kukura, P. Mass photometry enables label-free tracking and mass measurement of single proteins on lipid bilayers. Nat. Methods 2021, 18, 1247–1252.

[5]

Xu, M.; Tu, G. P.; Ji, M. W.; Wan, X. D.; Liu, J. J.; Liu, J.; Rong, H. P.; Yang, Y. L.; Wang, C.; Zhang, J. T. Vacuum-tuned-atmosphere induced assembly of Au@Ag core/shell nanocubes into multi-dimensional superstructures and the ultrasensitive IAPP proteins SERS detection. Nano Res. 2019, 12, 1375–1379.

[6]

Gruber, K.; Horlacher, T.; Castelli, R.; Mader, A.; Seeberger, P. H.; Hermann, B. A. Cantilever array sensors detect specific carbohydrate-protein interactions with picomolar sensitivity. ACS Nano 2011, 5, 3670–3678.

[7]

Dhayal, B.; Henne, W. A.; Doorneweerd, D. D.; Reifenberger, R. G.; Low, P. S. Detection of Bacillus subtilis spores using peptide-functionalized cantilever arrays. J. Am. Chem. Soc. 2006, 128, 3716–3721.

[8]

Watari, M.; Galbraith, J.; Lang, H. P.; Sousa, M.; Hegner, M.; Gerber, C.; Horton, M. A.; McKendry, R. A. Investigating the molecular mechanisms of in-plane mechanochemistry on cantilever arrays. J. Am. Chem. Soc. 2007, 129, 601–609.

[9]

Kosaka, P. M.; Pini, V.; Ruz, J. J.; Da Silva, R. A.; González, M. U.; Ramos, D.; Calleja, M.; Tamayo, J. Detection of cancer biomarkers in serum using a hybrid mechanical and optoplasmonic nanosensor. Nat. Nanotechnol. 2014, 9, 1047–1053.

[10]

Li, M.; Xi, N.; Wang, Y. C.; Liu, L. Q. Advances in atomic force microscopy for single-cell analysis. Nano Res. 2019, 12, 703–718.

[11]

Norman, L. L.; Badia, A. Redox actuation of a microcantilever driven by a self-assembled ferrocenylundecanethiolate monolayer: An investigation of the origin of the micromechanical motion and surface stress. J. Am. Chem. Soc. 2009, 131, 2328–2337.

[12]

Joo, J.; Kwon, D.; Yim, C.; Jeon, S. Highly sensitive diagnostic assay for the detection of protein biomarkers using microresonators and multifunctional nanoparticles. ACS Nano 2012, 6, 4375–4381.

[13]

Mader, A.; Gruber, K.; Castelli, R.; Hermann, B. A.; Seeberger, P. H.; Radler, J. O.; Leisner, M. Discrimination of Escherichia coli strains using glycan cantilever array sensors. Nano Lett. 2012, 12, 420–423.

[14]

Li, M.; Tang, H. X.; Roukes, M. L. Ultra-sensitive NEMS-based cantilevers for sensing, scanned probe and very high-frequency applications. Nat. Nanotechnol. 2007, 2, 114–120.

[15]

Wu, G. H.; Ji, H. F.; Hansen, K.; Thundat, T.; Datar, R.; Cote, R.; Hagan, M. F.; Chakraborty, A. K.; Majumdar, A. Origin of nanomechanical cantilever motion generated from biomolecular interactions. Proc. Natl. Acad. Sci. USA 2001, 98, 1560–1564.

[16]

Rodrigues, I. C.; Bothner, D.; Steele, G. A. Coupling microwave photons to a mechanical resonator using quantum interference. Nat. Commun. 2019, 10, 5359.

[17]

Eichelsdoerfer, D. J.; Liao, X.; Cabezas, M. D.; Morris, W.; Radha, B.; Brown, K. A.; Giam, L. R.; Braunschweig, A. B.; Mirkin, C. A. Large-area molecular patterning with polymer pen lithography. Nat. Protoc. 2013, 8, 2548–2560.

[18]

Yang, T. X.; Duncan, T. V. Challenges and potential solutions for nanosensors intended for use with foods. Nat. Nanotechnol. 2021, 16, 251–265.

[19]

Kasas, S.; Ruggeri, F. S.; Benadiba, C.; Maillard, C.; Stupar, P.; Tournu, H.; Dietler, G.; Longo, G. Detecting nanoscale vibrations as signature of life. Proc. Natl. Acad. Sci. USA 2015, 112, 378–381.

[20]

Ying, L. S.; Du, L. B.; Zou, R. Y.; Shi, L.; Zhang, N.; Jin, J. Y.; Xu, C. Y.; Zhang, F. R.; Zhu, C.; Wu, J. Z. et al. Development of a serum miRNA panel for detection of early stage non-small cell lung cancer. Proc. Natl. Acad. Sci. USA 2020, 117, 25036–25042.

[21]

Souza, P. C. T.; Alessandri, R.; Barnoud, J.; Thallmair, S.; Faustino, I.; Grünewald, F.; Patmanidis, I.; Abdizadeh, H.; Bruininks, B. M. H.; Wassenaar, T. A. et al. Martini 3: A general purpose force field for coarse-grained molecular dynamics. Nat. Methods 2021, 18, 382–388.

[22]

Tourancheau, A.; Mead, E. A.; Zhang, X. S.; Fang, G. Discovering multiple types of DNA methylation from bacteria and microbiome using nanopore sequencing. Nat. Methods 2021, 18, 491–498.

[23]

Janes, K. A.; Albeck, J. G.; Gaudet, S.; Sorger, P. K.; Lauffenburger, D. A.; Yaffe, M. B. A systems model of signaling identifies a molecular basis set for cytokine-induced apoptosis. Science 2005, 310, 1646–1653.

[24]

Kim, K.; Son, M.; Pak, Y.; Chee, S. S.; Auxilia, F. M.; Lee, B. K.; Lee, S.; Kang, S. K.; Lee, C.; Lee, J. S. et al. Erratum to: Charge transfer in graphene/polymer interfaces for CO2 detection. Nano Res. 2018, 11, 3957.

[25]

Wang, S.; Zhang, L. Q.; Wan, S.; Cansiz, S.; Cui, C.; Liu, Y.; Cai, R.; Hong, C. Y.; Teng, I. T.; Shi, M. et al. Aptasensor with expanded nucleotide using DNA nanotetrahedra for electrochemical detection of cancerous exosomes. ACS Nano 2017, 11, 3943–3949.

[26]

Wu, S. Q.; Liu, H.; Liang, X. M.; Wu, X. P.; Wang, B. M.; Zhang, Q. C. Highly sensitive nanomechanical immunosensor using half antibody fragments. Anal. Chem. 2014, 86, 4271–4277.

[27]

Rao, D. P.; Mei, K. N.; Yan, T. H.; Wang, Y.; Wu, W. J.; Chen, Y.; Wang, J. Y.; Zhang, Q. C.; Wu, S. Q. Nanomechanical sensor for rapid and ultrasensitive detection of tumor markers in serum using nanobody. Nano Res. 2022, 15, 1003–1012.

[28]

Backmann, N.; Zahnd, C.; Huber, F.; Bietsch, A.; Pluckthun, A.; Lang, H. P.; Guntherodt, H. J.; Hegner, M.; Gerber, C. A label-free immunosensor array using single-chain antibody fragments. Proc. Natl. Acad. Sci. USA 2005, 102, 14587–14592.

[29]

Liu, J. X.; Yan, L.; He, S. L.; Hu, J. Q. Engineering DNA quadruplexes in DNA nanostructures for biosensor construction. Nano Res. 2022, 15, 3504–3513.

[30]

Song, P.; Chen, S. X.; Yan, Y. H.; Pinto, A.; Cheng, L. Y.; Dai, P.; Patel, A. A.; Zhang, D. Y. Selective multiplexed enrichment for the detection and quantitation of low-fraction DNA variants via low-depth sequencing. Nat. Biomed. Eng. 2021, 5, 690–701.

[31]

Elledge, S. K.; Zhou, X. X.; Byrnes, J. R.; Martinko, A. J.; Lui, I.; Pance, K.; Lim, S. A.; Glasgow, J. E.; Glasgow, A. A.; Turcios, K. et al. Engineering luminescent biosensors for point-of-care SARS-CoV-2 antibody detection. Nat. Biotechnol. 2021, 39, 928–935.

[32]

Kurtz, D. M.; Soo, J.; Keh, L. C. T.; Alig, S.; Chabon, J. J.; Sworder, B. J.; Schultz, A.; Jin, M. C.; Scherer, F.; Garofalo, A. et al. Enhanced detection of minimal residual disease by targeted sequencing of phased variants in circulating tumor DNA. Nat. Biotechnol. 2021, 39, 1537–1547.

[33]

Zheng, G. F.; Patolsky, F.; Cui, Y.; Wang, W. U.; Lieber, C. M. Multiplexed electrical detection of cancer markers with nanowire sensor arrays. Nat. Biotechnol. 2005, 23, 1294–1301.

[34]

Hui, N.; Wang, J. S.; Wang, D. W.; Wang, P. P.; Luo, X. L.; Lv, S. P. An ultrasensitive biosensor for prostate specific antigen detection in complex serum based on functional signal amplifier and designed peptides with both antifouling and recognizing capabilities. Biosens. Bioelectron. 2022, 200, 113921.

[35]

Park, J.; Park, J. S.; Huang, C. H.; Jo, A.; Cook, K.; Wang, R.; Lin, H. Y.; Van Deun, J.; Li, H. Y.; Min, J. et al. An integrated magneto-electrochemical device for the rapid profiling of tumour extracellular vesicles from blood plasma. Nat. Biomed. Eng. 2021, 5, 678–689.

[36]

De La Rica, R.; Stevens, M. M. Plasmonic ELISA for the ultrasensitive detection of disease biomarkers with the naked eye. Nat. Nanotechnol. 2012, 7, 821–824.

[37]

Ning, B.; Huang, Z.; Youngquist, B. M.; Scott, J. W.; Niu, A.; Bojanowski, C. M.; Zwezdaryk, K. J.; Saba, N. S.; Fan, J.; Yin, X. M. et al. Liposome-mediated detection of SARS-CoV-2 RNA-positive extracellular vesicles in plasma. Nat. Nanotechnol. 2021, 16, 1039–1044.

[38]

Bull, M. S.; Sullan, R. M. A.; Li, H. B.; Perkins, T. T. Improved single molecule force spectroscopy using micromachined cantilevers. ACS Nano 2014, 8, 4984–4995.

[39]

Lim, C.; Huang, J.; Kim, S.; Lee, H.; Zeng, H. B.; Hwang, D. S. Nanomechanics of poly(catecholamine) coatings in aqueous solutions. Angew. Chem., Int. Ed. 2016, 55, 3342–3346.

[40]

Hamaker, H. C. The London-van der Waals attraction between spherical particles. Physica 1937, 4, 1058–1072.

[41]

London, F. The general theory of molecular forces. Trans. Faraday Soc. 1937, 33, 8b–26.

[42]

Zhou, J. Q.; Liang, Y. L.; He, X. W.; Chen, L. X.; Zhang, Y. K. Dual-functionalized magnetic metal-organic framework for highly specific enrichment of phosphopeptides. ACS Sustainable Chem. Eng. 2017, 5, 11413–11421.

[43]

Liu, Z.; Lei, S.; Zou, L. N.; Li, G. P.; Xu, L. L.; Ye, B. X. A label-free and double recognition-amplification novel strategy for sensitive and accurate carcinoembryonic antigen assay. Biosens. Bioelectron. 2019, 131, 113–118.

[44]

Yang, K.; Hu, Y. J.; Dong, N.; Zhu, G. C.; Zhu, T. F.; Jiang, N. J. A novel SERS-based magnetic aptasensor for prostate specific antigen assay with high sensitivity. Biosens. Bioelectron. 2017, 94, 286–291.

[45]

Lim, B.; Reddy, V.; Hu, X. H.; Kim, K. W.; Jadhav, M.; Abedini-Nassab, R.; Noh, Y. W.; Lim, Y. T.; Yellen, B. B.; Kim, C. G. Magnetophoretic circuits for digital control of single particles and cells. Nat. Commun. 2014, 5, 3846.

[46]

Hamaker, H. C. London-V. D. Waals forces in colloidal systems. Recl. Trav. Chim. Pays-Bas 1938, 57, 61–72.

[47]

Li, C.; Chen, X. J.; Zhang, Z.; Tang, J. L.; Zhang, B. L. Gold nanoparticle-DNA conjugates enhanced determination of dopamine by aptamer-based microcantilever array sensor. Sens. Actuators B: Chem. 2018, 275, 25–30.

[48]

Shu, W. M.; Laurenson, S.; Knowles, T. P. J.; Ferrigno, P. K.; Seshia, A. A. Highly specific label-free protein detection from lysed cells using internally referenced microcantilever sensors. Biosens. Bioelectron. 2008, 24, 233–237.

[49]

Zhou, M. H.; Meng, W. L.; Zhang, C. Y.; Li, X. B.; Wu, J. Z.; Zhang, N. H. The pH-dependent elastic properties of nanoscale DNA films and the resultant bending signals for microcantilever biosensors. Soft Matter 2018, 14, 3028–3039.

[50]

Rodriguez, M. L.; McGarry, P. J.; Sniadecki, N. J. Review on cell mechanics: Experimental and modeling approaches. Appl. Mech. Rev. 2013, 65, 060801.

[51]

Zhang, N. H.; Meng, W. L.; Tan, Z. Q. A multi-scale model for the analysis of the inhomogeneity of elastic properties of DNA biofilm on microcantilevers. Biomaterials 2013, 34, 1833–1842.

[52]

Zhang, N. H.; Tan, Z. Q.; Li, J. J.; Meng, W. L.; Xu, L. W. Interactions of single-stranded DNA on microcantilevers. Curr. Opin. Colloid Interface Sci. 2011, 16, 592–596.

[53]

Weizmann, Y.; Patolsky, F.; Katz, E.; Willner, I. Amplified DNA sensing and immunosensing by the rotation of functional magnetic particles. J. Am. Chem. Soc. 2003, 125, 3452–3454.

[54]

Weizmann, Y.; Patolsky, F.; Lioubashevski, O.; Willner, I. Magneto-mechanical detection of nucleic acids and telomerase activity in cancer cells. J. Am. Chem. Soc. 2004, 126, 1073–1080.

[55]

Ma, L. Y.; Wang, C. M.; Zhang, M. H. Detecting protein adsorption and binding using magnetic nanoparticle probes. Sens. Actuators B: Chem. 2011, 160, 650–655.

[56]

Blasberg, J. D.; Pass, H. I.; Goparaju, C. M.; Flores, R. M.; Lee, S.; Donington, J. S. Reduction of elevated plasma osteopontin levels with resection of non-small-cell lung cancer. J. Clin. Oncol. 2010, 28, 936–941.

Nano Research
Pages 3231-3239
Cite this article:
Rao D, Yan T, Qiao Z, et al. Relay-type sensing mode: A strategy to push the limit on nanomechanical sensor sensitivity based on the magneto lever. Nano Research, 2023, 16(2): 3231-3239. https://doi.org/10.1007/s12274-022-5049-0
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Received: 13 April 2022
Revised: 04 September 2022
Accepted: 14 September 2022
Published: 14 November 2022
© Tsinghua University Press 2022
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