Boosting the sub-cellular biomolecular cancer signals by self-functionalized tag-free nano sensor

Rupa Haldavnekar; Krishnan Venkatakrishnan; Dr Bo Tan

doi:10.1016/j.bios.2021.113407

Boosting the sub-cellular biomolecular cancer signals by self-functionalized tag-free nano sensor

Biosens Bioelectron. 2021 Oct 15:190:113407. doi: 10.1016/j.bios.2021.113407. Epub 2021 Jun 4.

Authors

Rupa Haldavnekar¹, Krishnan Venkatakrishnan², Dr Bo Tan³

Affiliations

¹ Institute for Biomedical Engineering, Science and Technology (iBEST), Toronto, Canada; Department of Mechanical and Industrial Engineering, Ryerson University, 350 Victoria Street, Toronto, ON, M5B 2K3, Canada; Nanocharacterization Laboratory, Department of Aerospace Engineering, Ryerson University, 350 Victoria Street, Toronto, ON, M5B 2K3, Canada; Department of Biomedical Engineering, Ryerson University, 350 Victoria Street, Toronto, ON, M5B 2K3, Canada.
² Keenan Research Center for Biomedical Science, St. Michael's Hospital, 30 Bond Street, Toronto, ON, M5B 1W8, Canada; Department of Mechanical and Industrial Engineering, Ryerson University, 350 Victoria Street, Toronto, ON, M5B 2K3, Canada; Nanocharacterization Laboratory, Department of Aerospace Engineering, Ryerson University, 350 Victoria Street, Toronto, ON, M5B 2K3, Canada; Department of Biomedical Engineering, Ryerson University, 350 Victoria Street, Toronto, ON, M5B 2K3, Canada. Electronic address: venkat@ryerson.ca.
³ Keenan Research Center for Biomedical Science, St. Michael's Hospital, 30 Bond Street, Toronto, ON, M5B 1W8, Canada; Department of Biomedical Engineering, Ryerson University, 350 Victoria Street, Toronto, ON, M5B 2K3, Canada.

PMID: 34134072
DOI: 10.1016/j.bios.2021.113407

Abstract

Surface Enhanced Raman Scattering (SERS)-based sub-cellular cancer diagnosis can simultaneously obtain multiple biomolecular signals crucial in diagnostic platform for a heterogeneous disease like cancer. But, SERS-probes being typically tagged with chemical functionalization demonstrate limitations due to adverse biocompatibility, ineffective cellular internalization, SERS-signal quenching and spectral contamination. Although, tag-free SERS-probes overcome these limitations; complexity in spectral interpretation and detection insensitivity make it disadvantageous. In this study, we have exploited the inherent charges of cellular biomolecules and introduced self-functionalized complementary charged, tag-free SERS nano probes for biomolecule-specific investigation. Extremely small nano probes (sub 10 nm), synthesized with multiphoton ionization were functionalized with charge by physical synthesis without any ligands or chemical processes. The probes demonstrated significant SERS (EF~10⁶) with analyte molecules (4ATP & 4MBA). Multifold signal boost was achieved for the signals of cellular components - amplification of ~7 fold for DNA, ~16 fold for proteins and ~24 fold for lipids with the commentary charged nano probes as compared to the neutral nano probes. The signal boost was attributed to the efficient delivery of extremely small, complementary charged probes to the cellular biomolecules of interest enabling simultaneous detection of sub-cellular biomolecules such as DNA, proteins and lipids and with high reproducibility. Cancer classification and investigation of drug resistance in cancer with single cell sensitivity was demonstrated. Such biomolecule-specific investigation of cancer from intact cells will open pathways for comprehensive cancer diagnosis.

Keywords: Biosensing; Cancer detection; Charged nano probes; SERS; Self-functionalized nano probes.

MeSH terms

Biosensing Techniques*
Gold
Humans
Metal Nanoparticles*
Neoplasms* / diagnosis
Neoplasms* / genetics
Reproducibility of Results

Substances

Gold