Plasmonic Single-Molecule Affinity Detection at 10<SUP>-20</SUP> Molar

Eleonora Macchia, Cinzia Di Franco, Cecilia Scandurra, Lucia Sarcina, Matteo Piscitelli, Michele Catacchio, Mariapia Caputo, Paolo Bollella, Gaetano Scamarcio*, Luisa Torsi*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

Abstract

DNA can be readily amplified through replication, enabling the detection of a single-target copy. A comparable performance for proteins in immunoassays has yet to be fully assessed. Surface-plasmon-resonance (SPR) serves as a probe capable of performing assays at concentrations typically around 10⁻⁹ molar. In this study, plasmonic single-molecule assays for both proteins and DNA are demonstrated, achieving limits-of-detections (LODs) as low as 10⁻2⁰ molar (1 ± 1 molecule in 0.1 mL), even in human serum, in 1 h. This represents an improvement in typical SPR LODs by eleven orders-of-magnitude. The single-molecule SPR assay is achieved with a millimeter-wide surface functionalized with a physisorbed biolayer comprising trillions of recognition-elements (antibodies or protein–probe complexes) which undergo an acidic or alkaline pH-conditioning. Potentiometric and surface-probing imaging experiments reveal the phenomenon underlying this extraordinary performance enhancement. The data suggest an unexplored amplification process within the biomaterial, where pH-conditioning, driving the biolayer in a metastable state, induces a self-propagating aggregation of partially misfolded proteins, following single-affinity binding. This process triggers an electrostatic rearrangement, resulting in the displacement of a charge equivalent to 1.5e per 102 recognition elements. Such findings open new opportunities for reliable SPR-based biosensing at the physical detection limits, with promising applications in point-of-care plasmonic systems.
Original languageEnglish
Article number2418610
Number of pages15
JournalAdvanced Materials
DOIs
Publication statusPublished - 23 Jan 2025
MoE publication typeA1 Journal article-refereed

Keywords

  • Plasmonic sensors
  • Single-molecule sensing
  • single-molecule with a large transistor (SiMoT)
  • Surface probing techniques
  • Surface-plasmon-resonance

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