Table 3.
Comparison of WGM Single Molecule Biosensing to a Selection of Other Technology Platforms
| Sensor [Example Ref.] | WGM, Plasmon Enhanced [4,167] | Nano-Plasmonics [9,11] | Nanopores [303–305] | Zero-Mode Waveguide [306] | Carbon Nanotube Field-Effect Transistor [6] |
|---|---|---|---|---|---|
| Sensor domain | optical | optical | electrical | optical | electrical |
| Sensor structure | glass microsphere+plasmonic nanoparticle |
plasmonic nanoparticle (nanorod) |
alpha-hemolysine or solid-state nanopore |
zero-mode metal-clad waveguide with fluorescence excitation and readout capability |
carbon nanotube field-effect transistor |
| Specificity | directly monitoring specific interaction kinetics of a receptor, i.e., a short oligonucleotide receptor |
by monitoring binding events to high affinity receptors such as streptavidin |
modified for specific detection; analyte binding results in pore blockage; sequencing from sensor response during DNA translocation; sequencing by digestions |
monitoring enzyme kinetics using fluorescent labels, i.e., DNA polymerase using fluorescent nucleotide analogs for sequencing applications |
directly monitoring specific interaction kinetics of a receptor, i.e., a short oligonucleotide receptor |
| Current sensitivity | <2.4 kDa short oligonucleotide, <1 kDa intercalating molecules |
~50 kDa protein (streptavidin) |
single nucleotide in sequencing by digestion approach |
single fluorescently labeled nucleotide |
short oligonucleotide |
| Current time resolution | limited by Q-factor, ~100 ns | ~ms | ~sub-ms | ~ms | ~ms |
| Multiplexing | yes | yes | yes | yes | yes |
| Receptor molecule properties |
transient interactions are monitored; use of nonconventional receptors, e.g., short oligonucleotides, enzymes, low affinity receptors, possible |
demonstrations thus far use high affinity receptors |
nanopore only, where specific detection relies, i.e., on sequencing by digestion or on modification of the nanopore with specific analyte binding sites |
fluorescence labeling required; DNA sequencing has been demonstrated |
transient interactions can be monitored, demonstrated for short oligonucleotide receptors monitored at different temperatures |
| Sensor lifetime | extended sensor lifetime, limited by receptor kinetics and lifetime; no saturation of receptor required |
detection requires saturation of receptor |
extended sensor lifetime, limited by blockage of pore |
limited by lifetime of polymerase | no saturation of receptor molecules is required |