Label-free molecular diagnosis and biosensor

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One-step homogeneous detection assay with dual color light scattering on nanoparticles

Principal investigator : Jerome Wenger, Stéphanie Vial

We introduce a novel technique for high sensitivity specific molecular biosensing in a single step homogeneous solution phase. Our approach is based on dual-color illumination and detection of the scattering intensities from silver and gold nanoparticles. In the absence of the target molecule, the silver and gold nanoparticles move independently and their respective scattering signals are uncorrelated. The presence of the target molecule induces aggregation between the probe-functionalized nanoparticles, and thus silver and gold nanoparticles diffuse and scatter light simultaneously. This gives rise to temporal coincidences which quantify the amount of target molecule. To demonstrate the efficiency of our technique, we detect a specific DNA sequence for a range of concentration from 5 pM to 1.5 nM with a limit of detection of 1 pM. Our method is sensitive and specific enough to detect single nucleotide deletion and mismatch.

Key features of our technology :

  • Fast : single mixing step, 30 minutes incubation, less than one minute optical readout
  • Simple : minimal manipulation, no grafting on surface, no rinsing
  • Sensitive : limit of detection typically below 1 pM or 10 pg/mL
  • Accurate : specific to the target, single nucleotide deletion or mismatch
  • Low sample volume : typically less than 10 microliters at pM concentration
  • Low noise : the optical scattering of nanoparticles is million times brighter than fluorescent molecules and not limited by photobleaching

Want to learn more ? See our pdf presentation slides here

Publications

[2] S. Vial, J. Wenger, Single-step homogeneous immunoassay for detecting prostate-specific antigen using dual-color light scattering of metal nanoparticles, Analyst 142, 3484-3491 (2017).
[1] S. Vial, Y. Berrahal, M. Prado, J. Wenger, Single-Step DNA Detection Assay Monitoring Dual-Color Light Scattering from Individual Metal Nanoparticle Aggregates, ACS Sensors 2, 251-256 (2017).

Patents

Detection of analytes using nanoparticles as light scattering enhancers, WO2016046335 A1, Wenger J., Rigneault H.

This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 664738 PhoCCS).