DOI: 10.1002/ejic.202300288 ISSN:

Lanthanide‐FRET molecular beacons for microRNA biosensing, logic operations, and physical unclonable functions

Mariia Dekaliuk, Niko Hildebrandt
  • Inorganic Chemistry

Time‐resolved or time‐gated (TG) biosensing and bioimaging with luminescent lanthanide probes and Förster resonance energy transfer (FRET) have significantly advanced bioanalytical chemistry. However, the development of lanthanide‐based molecular beacons (MBs) has been rather limited. Here, we designed DNA stem‐loop MB probes against two different microRNAs (miR‐21 and miR‐27b) using Tb and Eu FRET donors and quenching (BHQ2) and fluorescent (Cy3) FRET acceptors. Limits of detection down to 190 pM and duplexed miR‐21/miR‐27b quantification at low nanomolar concentrations with Tb‐BHQ2 and Eu‐BHQ2 TG‐FRET MBs demonstrated the versatility and high analytical performance of lanthanide‐based MBs. The particular donor‐acceptor distances in the Tb‐Cy3 MB resulted in inverted nucleic acid target concentration‐dependent TG PL intensities in short and long TG detection windows after pulsed excitation. We showed that this specific feature of our TG‐FRET MBs can be adapted to the design of molecular logic devices (NOR, OR, NAND, AND, XNOR, XOR, IMPLEMENT, and INHIBIT). Moreover, the almost unlimited choice of TG detection windows and the distinct spectral features of Tb and Cy3 over a broad visible spectral range could be exploited to devise biophotonic physical unclonable functions for highly secure authentication and identification. Our study manifests the versatility of lanthanides for advanced biophotonic applications.

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