Remote Detection of Biomolecules on Surfaces

Below is a tour of the main non‑contact, line‑of‑sight techniques that researchers have tried—or are actively developing—to see whether a specific biomolecule (e.g. a SARS‑CoV‑2 protein) is present on a surface. I order them (very roughly) from the most mature to the most speculative and note typical stand‑off ranges, selectivity, and the biggest technical hurdles.


1. Laser‑Induced Fluorescence (LIF) & LIF‑LiDAR

How it works. A UV (or multi‑wavelength) laser excites intrinsic fluorophores such as aromatic amino‑acids, NADH, FAD, etc. The time‑resolved and multi‑band fluorescence signature is collected with a telescope and classified.
Status. Laboratory LIF‑LiDAR rigs have distinguished MS2 bacteriophage from background aerosols and detected viral contamination on stainless‑steel a few metres away. Field systems exist for bacterial spores, pollen, and fungi.
Limits. Fluorescence spectra of viruses differ only subtly from many other biomaterials, so one usually gets “something biological here” rather than “this is SARS‑CoV‑2”. Surface roughness and environmental light add noise.


2. Raman‑based Stand‑off Spectroscopy

VariantTypical rangeWhat’s been shownKey advantageKey limitation
Spontaneous Raman (cw/pulsed)0.2–2 m (lab)Generic bio‑residue IDDirect molecular “fingerprint”Very weak signal → long integration & high‑power lasers
Surface‑Enhanced Raman (SERS)cm–m if the contaminated surface already carries metallic nanostructurespg‑level viral RNA on engineered chipsHuge signal boostNeeds SERS substrate on the surface, so not purely stand‑off
Coherent anti‑Stokes Raman (CARS/SRS)1 m demonstrated for Bacillus spores at 10^5 cfu mm‑2 in 1 sHigh S/N, fastBulky fs‑laser benches; virus signal even weaker than spores

For a naked surface that someone cough‑contaminated, CARS is currently the most promising path to single‑shot molecular specificity, but no team has yet published a clear SARS‑CoV‑2 CARS spectrum at distance.


3. Terahertz (THz) Time‑Domain & Metamaterial Sensors

THz waves (0.1‑10 THz) couple to collective vibrations of proteins and nucleic acids. Metamaterial resonators shift in frequency when a target antigen binds, and those shifts can be read remotely with a THz beam. Lab chips have detected femtomolar levels of SARS‑CoV‑2 spike protein on a substrate — no labels, no reagents.
Reality check: today the analyte has to sit on the metamaterial for the shift to be measurable; projecting a THz pulse at an ordinary doorknob and picking out a 100‑nm viral monolayer is still a theory paper.


4. Infra‑red / Open‑Path FTIR

Mid‑IR absorption gives rich chemical information and commercial open‑path FTIR instruments can spot organic films or nerve‑agent residues on walls tens of metres away. Viral proteins absorb too, but the signal from a monolayer is far below current detection limits once you fold in atmospheric water and thermal background.


5. Photoacoustic & Photothermal Stand‑off Sensing

A nanosecond laser pulse heats the contaminant; the rapid expansion makes an acoustic wave or modulates a probe beam. Array microphones or interferometers a few metres away pick up the signature. The technique works for micrometre‑thick explosive films and theoretically scales to biological layers. www.mdpi.comwww.sciencedirect.com Sensitivity and selectivity for sub‑micron viral films remain unproven.


6. Laser‑Induced Breakdown Spectroscopy (LIBS)

A high‑energy pulse ablates a micro‑spot; the plasma emission lines reveal elemental composition. Portable LIBS units mounted on robots have discriminated bacterial versus mineral films at 3–5 m. pmc.ncbi.nlm.nih.gov That elemental fingerprint is not specific to a given virus, and the shot is destructive, but LIBS can quickly flag “organic / nitrogen‑rich material here—check further.”


7. Speculative / Early‑Stage Ideas

  • Quantum cascade laser heterodyne IR: promises part‑per‑trillion path‑length–normalised absorbance, but noise floors for monolayers are unknown.
  • Remote evanescent‑field sensors using airborne nanodrones (spray the surface with functional nanoparticles, then read reflectance changes). Effective, but violates the “no altering the surface” condition.
  • Machine‑learning hyperspectral imagers (VIS‑SWIR) trained on large contaminant libraries. Good for broad bio‑vs‑non‑bio flags, unlikely for agent‑level ID without a tagging layer.

Why it’s so hard

  • Signal strength scales with molecular surface density. A smooth steel handle contaminated by a sneeze carries <10 ng cm‑2 of viral protein—orders of magnitude below most stand‑off demonstration loads.
  • Spectral congestion & background. Proteins, pollen, skin oils, food residues and plastics share many vibrational and fluorescence bands; disentangling them at low S/N is a real challenge.
  • Laser safety & eye‑safe power. Pushing enough photons onto the spot without exceeding ANSI eye limits (or igniting dust) is non‑trivial.
  • Orientation & surface roughness. A rough paint layer scatters the beam and broadens the Raman/IR line‑shape, lowering specificity.

Practical takeaway (2025)

  • Today – No fieldable instrument can look at an arbitrary surface and say “SARS‑CoV‑2 detected” without first wiping or swabbing.
  • Near‑term (3‑5 yrs) – Compact femtosecond‑laser CARS/LIF hybrids and chip‑scale THz imagers may reach the sensitivity to flag some high‑loading biofilms on smooth surfaces at 1‑2 m.
  • Long‑term – True single‑virus, non‑contact surface detection probably demands either (a) active deposition of enhancers (nanoparticles, tagged antibodies) or (b) a breakthrough in quantum‑enhanced vibrational spectroscopy well beyond current TRL. For now, surface swabs plus PCR or immuno‑assay remain the gold standard, but watch the ultrafast Raman/CARS and THz‑metamaterial communities—they’re closing the gap fastest.