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Ultrasensitive Label-Free Nucleic-Acid Biosensors Based on Bimodal Waveguide Interferometers

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Biomedical Engineering Technologies

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2393))

Abstract

The bimodal waveguide (BiMW) biosensor is an innovative common path interferometric sensor based on the evanescent field detection principle. This biosensor allows for the direct detection of virtually any biomolecular interaction in a label-free scheme by using specific biorecognition elements. Due to its inherent ultrasensitivity, it has been employed for the monitoring of relevant nucleic-acid sequences such as mRNA transcripts or microRNAs present at the attomolar–femtomolar concentration level in human samples. The application of the BiMW biosensor to detect these nucleic acids can be a powerful analytical tool for diagnosis and prognosis of complex illnesses, such as cancer, where these biomarkers play a major role. The BiMW sensor is fabricated using standard silicon-based microelectronics technology, which allows its miniaturization and cost-effective production, meeting the requirements of portability and disposability for the development of point-of-care (PoC) sensing platforms.

In this chapter, we describe the working principle of the BiMW biosensor as well as its application for the analysis of nucleic acids. Concretely, we show a detailed description of DNA functionalization procedures and the complete analysis of two different RNA biomarkers for cancer diagnosis: (1) the analysis of mRNA transcripts generated by alternative splicing of Fas gene, and (2) the detection of miRNA 181a from urine liquid biopsies, for the early diagnosis of bladder cancer. The biosensing detection is performed by a direct assay in real time, by monitoring the changes in the intensity pattern of the light propagating through the BiMW biosensor, due to the hybridization of the target with the specific DNA probe previously functionalized on the BiMW sensor surface.

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Acknowledgments

ICN2 is supported by the “Severo Ochoa Centers of Excellence” Program from the Spanish Ministry of Science (MINECO) (Grant No. SEV-2017-0706).

Dr. Cesar S. Huertas is a recipient of an RMIT Vice Chancellor’s Postdoctoral Fellowship.

A substantial part of the content of this chapter has been adapted from a previous version of this chapter [24] the doctoral thesis Nanophotonics biosensors for deciphering cell regulation pathways [21].

Author information

Authors and Affiliations

  1. Integrated Photonics and Applications Centre, School of Engineering, RMIT University, Melbourne, VIC, Australia

    Cesar S. Huertas

  2. Nanobiosensors and Bioanalytical Applications Group, Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC, BIST and CIBER-BBN, Campus UAB, Ed-ICN2, Barcelona, Spain

    Laura M. Lechuga

Authors
  1. Cesar S. Huertas
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  2. Laura M. Lechuga
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Corresponding author

Correspondence to Cesar S. Huertas .

Editor information

Editors and Affiliations

  1. Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, MD, USA

    Miguel R. Ossandon

  2. Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD, USA

    Houston Baker

  3. Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD, USA

    Avraham Rasooly

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Huertas, C.S., Lechuga, L.M. (2022). Ultrasensitive Label-Free Nucleic-Acid Biosensors Based on Bimodal Waveguide Interferometers. In: Ossandon, M.R., Baker, H., Rasooly, A. (eds) Biomedical Engineering Technologies. Methods in Molecular Biology, vol 2393. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1803-5_6

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  • DOI: https://doi.org/10.1007/978-1-0716-1803-5_6

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1802-8

  • Online ISBN: 978-1-0716-1803-5

  • eBook Packages: Springer Protocols

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