Skip to main content
SpringerLink
Log in

Dynamic light scattering biosensing based on analyte-induced inhibition of nanoparticle aggregation

  • Research Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

A new approach to direct quantitative detection of small molecules (haptens) by dynamic light scattering biosensing is presented. The proposed technique implements a homogeneous competitive immunoassay and is based on optical detection of specific inhibition of nanoparticle aggregation induced by the analyte in a sample. The technique performance was tested both in buffer and milk for detection of chloramphenicol – antibiotic relevant to food safety diagnostics. Good specificity, sensitivity (LOD in milk is 2.4 ng/ml), precision (4.0 ± 1.2%), ruggedness (8.3%), and 96% recovery in conjunction with a record wide dynamic range (3 orders of magnitude) of the nanosensing technique were demonstrated. Such characteristics complemented by the assay simplicity (no washing step) and a short assay time make the approach attractive for application as an analytical platform for point-of-care and field-oriented diagnostics.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Wolfbeis OS. Optical technology until the year 2000: an historical overview. In: Optical sensors. Berlin: Springer Berlin Heidelberg; 2004. p. 1–34.

    Google Scholar 

  2. Nikitin PI, Beloglazov AA. A multi-purpose sensor based on surface plasmon polariton resonance in a Schottky structure. Sensors Actuators A Phys. 1994;42:547–52. https://doi.org/10.1016/0924-4247(94)80051-0.

    Article  CAS  Google Scholar 

  3. Gauglitz G, Homola J. Direct optical detection. Anal Bioanal Chem. 2015;407:3881–2. https://doi.org/10.1007/s00216-015-8577-6.

    Article  CAS  PubMed  Google Scholar 

  4. Zourob M, Elwary S, Turner A. Principles of bacterial detection: biosensors, recognition receptors and microsystems. New York: Springer New York; 2008.

    Book  Google Scholar 

  5. Du B-A, Li Z-P, Liu C-H. One-step homogeneous detection of DNA hybridization with gold nanoparticle probes by using a linear light-scattering technique. Angew Chem Int Ed. 2006;45:8022–5. https://doi.org/10.1002/anie.200603331.

    Article  CAS  Google Scholar 

  6. Liu X, Dai Q, Austin L, Coutts J, Knowles G, Zou J, et al. A one-step homogeneous immunoassay for cancer biomarker detection using gold nanoparticle probes coupled with dynamic light scattering. J Am Chem Soc. 2008;130:2780–2. https://doi.org/10.1021/ja711298b.

    Article  CAS  PubMed  Google Scholar 

  7. Huang X, Xu Z, Mao Y, Ji Y, Xu H, Xiong Y, et al. Gold nanoparticle-based dynamic light scattering immunoassay for ultrasensitive detection of Listeria monocytogenes in lettuces. Biosens Bioelectron. 2015;66:184–90. https://doi.org/10.1016/j.bios.2014.11.016.

    Article  CAS  PubMed  Google Scholar 

  8. Dai Q, Liu X, Coutts J, Austin L, Huo Q. A one-step highly sensitive method for DNA detection using dynamic light scattering. J Am Chem Soc. 2008;130:8138–9. https://doi.org/10.1021/ja801947e.

    Article  CAS  PubMed  Google Scholar 

  9. Kalluri JR, Arbneshi T, Afrin Khan S, Neely A, Candice P, Varisli B, et al. Use of gold nanoparticles in a simple colorimetric and ultrasensitive dynamic light scattering assay: selective detection of arsenic in groundwater. Angew Chem Int Ed. 2009;48:9668–71. https://doi.org/10.1002/anie.200903958.

    Article  CAS  Google Scholar 

  10. Borisov SM, Wolfbeis OS. Optical biosensors. Chem Rev. 2008;108:423–61. https://doi.org/10.1021/cr068105t.

    Article  CAS  PubMed  Google Scholar 

  11. Nikitin MP, Shipunova VO, Deyev SM, Nikitin PI. Biocomputing based on particle disassembly. Nat Nanotechnol. 2014;9:716–22. https://doi.org/10.1038/nnano.2014.156.

    Article  CAS  PubMed  Google Scholar 

  12. Tregubov AA, Nikitin PI, Nikitin MP. Advanced smart nanomaterials with integrated logic-gating and biocomputing: dawn of theranostic nanorobots. Chem Rev. 2018;118:10294–348. https://doi.org/10.1021/acs.chemrev.8b00198.

    Article  CAS  PubMed  Google Scholar 

  13. Sokolov IL, Cherkasov VR, Tregubov AA, Buiucli SR, Nikitin MP. Smart materials on the way to theranostic nanorobots: molecular machines and nanomotors, advanced biosensors, and intelligent vehicles for drug delivery. Biochim Biophys Acta Gen Subj. 2017;1861:1530–44. https://doi.org/10.1016/j.bbagen.2017.01.027.

    Article  CAS  PubMed  Google Scholar 

  14. Cherkasov VR, Mochalova EN, Babenyshev AV, Vasilyeva AV, Nikitin PI, Nikitin MP. Nanoparticle beacons: supersensitive smart materials with on/off-switchable affinity to biomedical targets. ACS Nano. 2020;14:1792–803. https://doi.org/10.1021/acsnano.9b07569.

    Article  CAS  PubMed  Google Scholar 

  15. Jans H, Liu X, Austin L, Maes G, Huo Q. Dynamic light scattering as a powerful tool for gold nanoparticle bioconjugation and biomolecular binding studies. Anal Chem. 2009;81:9425–32. https://doi.org/10.1021/ac901822w.

    Article  CAS  PubMed  Google Scholar 

  16. Zheng T, Bott S, Huo Q. Techniques for accurate sizing of gold nanoparticles using dynamic light scattering with particular application to chemical and biological sensing based on aggregate formation. ACS Appl Mater Interfaces. 2016;8:21585–94. https://doi.org/10.1021/acsami.6b06903.

    Article  CAS  PubMed  Google Scholar 

  17. Seow N, Tan YN, Yung L-YL. Gold nanoparticle-dynamic light scattering tandem for the rapid and quantitative detection of the let7 microRNA family. Part Part Syst Charact. 2014;31:1260–8. https://doi.org/10.1002/ppsc.201400158.

    Article  CAS  Google Scholar 

  18. Seow N, Tan YN, Yung L-YL SX. DNA-directed assembly of nanogold dimers: a unique dynamic light scattering sensing probe for transcription factor detection. Sci Rep. 2016;5:18293. https://doi.org/10.1038/srep18293.

    Article  CAS  Google Scholar 

  19. Li C, Ma J, Fan Q, Tao Y, Li G. Dynamic light scattering (DLS)-based immunoassay for ultra-sensitive detection of tumor marker protein. Chem Commun. 2016;52:7850–3. https://doi.org/10.1039/C6CC02633H.

    Article  CAS  Google Scholar 

  20. Zheng T, Pierre-Pierre N, Yan X, Huo Q, Almodovar AJO, Valerio F, et al. Gold nanoparticle-enabled blood test for early stage cancer detection and risk assessment. ACS Appl Mater Interfaces. 2015;7:6819–27. https://doi.org/10.1021/acsami.5b00371.

    Article  CAS  PubMed  Google Scholar 

  21. Mustafaoglu N, Kiziltepe T, Bilgicer B. Site-specific conjugation of an antibody on a gold nanoparticle surface for one-step diagnosis of prostate specific antigen with dynamic light scattering. Nanoscale. 2017;9:8684–94. https://doi.org/10.1039/C7NR03096G.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Huo Q, Litherland SA, Sullivan S, Hallquist H, Decker DA, Rivera-Ramirez I. Developing a nanoparticle test for prostate cancer scoring. J Transl Med. 2012;10:44. https://doi.org/10.1186/1479-5876-10-44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Driskell JD, Jones CA, Tompkins SM, Tripp RA. One-step assay for detecting influenza virus using dynamic light scattering and gold nanoparticles. Analyst. 2011;136:3083. https://doi.org/10.1039/c1an15303j.

    Article  CAS  PubMed  Google Scholar 

  24. Zheng T, Finn C, Parrett CJ, Dhume K, Hwang JH, Sidhom D, et al. A rapid blood test to determine the active status and duration of acute viral infection. ACS Infect Dis. 2017;3:866–73. https://doi.org/10.1021/acsinfecdis.7b00137.

    Article  CAS  PubMed  Google Scholar 

  25. Lai YH, Koo S, Oh SH, Driskell EA, Driskell JD. Rapid screening of antibody–antigen binding using dynamic light scattering (DLS) and gold nanoparticles. Anal Methods. 2015;7:7249–55. https://doi.org/10.1039/C5AY00674K.

    Article  CAS  Google Scholar 

  26. Gao D, Sheng Z, Han H. An ultrasensitive method for the detection of gene fragment from transgenics using label-free gold nanoparticle probe and dynamic light scattering. Anal Chim Acta. 2011;696:1–5. https://doi.org/10.1016/j.aca.2011.04.001.

    Article  CAS  PubMed  Google Scholar 

  27. Fu C, Ma H, Huang C, Jia N. A simple and dual functional dynamic light scattering (DLS) probe for rapid detection of mercury ions and biothiols. Anal Methods. 2015;7:7455–60. https://doi.org/10.1039/C5AY01880C.

    Article  CAS  Google Scholar 

  28. Huang X, Liu Y, Yung B, Xiong Y, Chen X. Nanotechnology-enhanced no-wash biosensors for in vitro diagnostics of cancer. ACS Nano. 2017;11:5238–92. https://doi.org/10.1021/acsnano.7b02618.

    Article  CAS  PubMed  Google Scholar 

  29. Orlov AV, Nikitin MP, Bragina VA, Znoyko SL, Zaikina MN, Ksenevich TI, et al. A new real-time method for investigation of affinity properties and binding kinetics of magnetic nanoparticles. J Magn Magn Mater. 2015;380:231–5. https://doi.org/10.1016/j.jmmm.2014.10.019.

    Article  CAS  Google Scholar 

  30. Ivanov AE, Pushkarev AV, Orlov AV, Nikitin MP, Nikitin PI. Interferometric detection of chloramphenicol via its immunochemical recognition at polymer-coated nano-corrugated surfaces. Sensors Actuators B Chem. 2019;282:984–91. https://doi.org/10.1016/j.snb.2018.11.043.

    Article  CAS  Google Scholar 

  31. Sai N, Chen Y, Liu N, Yu G, Su P, Feng Y, et al. A sensitive immunoassay based on direct hapten coated format and biotin–streptavidin system for the detection of chloramphenicol. Talanta. 2010;82:1113–21. https://doi.org/10.1016/j.talanta.2010.06.018.

    Article  CAS  PubMed  Google Scholar 

  32. Brox S, Ritter AP, Küster E, Reemtsma T. A quantitative HPLC–MS/MS method for studying internal concentrations and toxicokinetics of 34 polar analytes in zebrafish (Danio rerio) embryos. Anal Bioanal Chem. 2014;406:4831–40. https://doi.org/10.1007/s00216-014-7929-y.

    Article  CAS  PubMed  Google Scholar 

  33. Dams ET, Laverman P, Oyen WJ, Storm G, Scherphof GL, van Der Meer JW, et al. Accelerated blood clearance and altered biodistribution of repeated injections of sterically stabilized liposomes. J Pharmacol Exp Ther. 2000;292:1071–9.

    CAS  PubMed  Google Scholar 

  34. Sun M, Ding B, Lin J, Yu J, Sun G. Three-dimensional sensing membrane functionalized quartz crystal microbalance biosensor for chloramphenicol detection in real time. Sensors Actuators B Chem. 2011;160:428–34. https://doi.org/10.1016/j.snb.2011.08.004.

    Article  CAS  Google Scholar 

  35. Amjadi M, Jalili R, Manzoori JL. A sensitive fluorescent nanosensor for chloramphenicol based on molecularly imprinted polymer-capped CdTe quantum dots. Luminescence. 2016;31:633–9. https://doi.org/10.1002/bio.3003.

    Article  CAS  PubMed  Google Scholar 

  36. Xie Y, Zhao M, Hu Q, Cheng Y, Guo Y, Qian H, et al. Selective detection of chloramphenicol in milk based on a molecularly imprinted polymer-surface-enhanced Raman spectroscopic nanosensor. J Raman Spectrosc. 2017;48:204–10. https://doi.org/10.1002/jrs.5034.

    Article  CAS  Google Scholar 

  37. Javidi M, Housaindokht MR, Verdian A, Razavizadeh BM. Detection of chloramphenicol using a novel apta-sensing platform based on aptamer terminal-lock in milk samples. Anal Chim Acta. 2018;1039:116–23. https://doi.org/10.1016/j.aca.2018.07.041.

    Article  CAS  PubMed  Google Scholar 

  38. Wu Y, Liu B, Huang P, Wu F-Y. A novel colorimetric aptasensor for detection of chloramphenicol based on lanthanum ion–assisted gold nanoparticle aggregation and smartphone imaging. Anal Bioanal Chem. 2019. https://doi.org/10.1007/s00216-019-02149-7.

    Article  CAS  Google Scholar 

  39. Saha B, Evers TH, Prins MWJ. How antibody surface coverage on nanoparticles determines the activity and kinetics of antigen capturing for biosensing. Anal Chem. 2014;86:8158–66. https://doi.org/10.1021/ac501536z.

    Article  CAS  PubMed  Google Scholar 

  40. Gambinossi F, Mylon SE, Ferri JK. Aggregation kinetics and colloidal stability of functionalized nanoparticles. Adv Colloid Interf Sci. 2015;222:332–49. https://doi.org/10.1016/j.cis.2014.07.015.

    Article  CAS  Google Scholar 

  41. Holthoff H, Egelhaaf SU, Borkovec M, Schurtenberger P, Sticher H. Coagulation rate measurements of colloidal particles by simultaneous static and dynamic light scattering. Langmuir. 1996;12:5541–9. https://doi.org/10.1021/la960326e.

    Article  CAS  Google Scholar 

  42. Shevchenko KG, Cherkasov VR, Nikitina IL, Babenyshev AV, Nikitin MP. Smart multifunctional nanoagents for in situ monitoring of small molecules with a switchable affinity towards biomedical targets. Appl Nanosci. 2018;8:195–203. https://doi.org/10.1007/s13204-018-0659-2.

    Article  CAS  Google Scholar 

  43. Guteneva NV, Znoyko SL, Orlov AV, Nikitin MP, Nikitin PI. Rapid lateral flow assays based on the quantification of magnetic nanoparticle labels for multiplexed immunodetection of small molecules: application to the determination of drugs of abuse. Microchim Acta. 2019;186:621. https://doi.org/10.1007/s00604-019-3726-9.

    Article  CAS  Google Scholar 

  44. Shevchenko KG, Cherkasov VR, Tregubov AA, Nikitin PI, Nikitin MP. Surface plasmon resonance as a tool for investigation of non-covalent nanoparticle interactions in heterogeneous self-assembly & disassembly systems. Biosens Bioelectron. 2017;88:3–8. https://doi.org/10.1016/j.bios.2016.09.042.

    Article  CAS  PubMed  Google Scholar 

  45. Levin AD, Shmytkova EA. Nonspherical nanoparticles characterization by partially depolarized dynamic light scattering. Proc SPIE. 2015;9526:95260P. https://doi.org/10.1117/12.2184867.

    Article  Google Scholar 

  46. National Center for Biotechnology Information (accessed on Mar. 12, 2020) PubChem Database. Chloramphenicol, CID=5959, https://pubchem.ncbi.nlm.nih.gov/compound/Chloramphenicol.

Download references

Funding

This multidisciplinary work was supported by the grant of Russian Science Foundation no. 16-19-00131 (development and characterization of the nanoparticles and their conjugates with bioreceptors) and Ministry of Science and Higher Education of Russian Federation in the framework of the implementation of agreement no. 14.624.21.0045 of September 26, 2017 (unique identifier RFMEFI62417X0045) (dynamic light scattering assay experiments).

Author information

Author notes

  1. A. D. Levin and A. Ringaci contributed equally to this work.

Authors and Affiliations

  1. All-Russian Research Institute for Optical and Physical Measurements, 46 Ozernaya st., 119361, Moscow, Russia

    A. D. Levin, M. K. Alenichev & E. B. Drozhzhennikova

  2. Moscow Institute of Physics and Technology, 9 Institutskii per., 141700, Dolgoprudny, Moscow Region, Russia

    A. Ringaci, K. G. Shevchenko, V. R. Cherkasov & M. P. Nikitin

  3. Prokhorov General Physics Institute of the Russian Academy of Sciences, 38 Vavilov St, 119991, Moscow, Russia

    K. G. Shevchenko, V. R. Cherkasov & P. I. Nikitin

Authors
  1. A. D. Levin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Ringaci
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. K. Alenichev
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. B. Drozhzhennikova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K. G. Shevchenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. V. R. Cherkasov
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. P. Nikitin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. P. I. Nikitin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to A. D. Levin or M. P. Nikitin.

Ethics declarations

Conflict of interest

All-Russian Research Institute for Optical and Physical Measurements has filed a patent application RU2019140681 on the developed assay technology (L.A.D., R.A., A.M.K., D.E.B., N.M.P. are named as the inventors).

Additional information

Published in the topical collection Advances in Direct Optical Detection with guest editors Antje J. Baeumner, Günter Gauglitz, and Jiri Homola.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(PDF 609 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Levin, A.D., Ringaci, A., Alenichev, M.K. et al. Dynamic light scattering biosensing based on analyte-induced inhibition of nanoparticle aggregation. Anal Bioanal Chem 412, 3423–3431 (2020). https://doi.org/10.1007/s00216-020-02605-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-020-02605-9

Keywords

Search

Navigation