NanoSE: How We Co-Developed a Dual-Readout Biosensor — From Pesticides to a Pandemic

Most of the research we feature was done by independent labs who simply chose our instruments. This one is different: our own people are on the author lists, and the platform they helped build is traceable across three years and three escalating problems — a pesticide, a blood biomarker, and a virus.

A single-signal biosensor makes you choose. Surface-enhanced Raman scattering (SERS) gives a molecule’s exact vibrational fingerprint — unambiguous identity — but can be unforgiving at the lowest concentrations. Plasmon-enhanced fluorescence (PEF, also called SPEF) gives enormous brightness and a fast, quantitative readout, but not a fingerprint. For years a lab building a point-of-care test had to pick one and live with its blind spot.

The obvious idea — get both signals from one chip — runs into a hard fabrication problem: SERS and PEF want different things from a metal nanostructure, and a substrate optimized for one usually compromises the other. Between 2016 and 2023, a collaboration centered on Cheng-Chung Chang’s group at National Chung Hsing University — with Protrustech and, later, Nanovie staff as named co-authors — worked that problem into a platform that does both at once from a single silver-nanowire chip. That platform is NanoSE, and this is the story of how it grew up.

The Obstacle — Two Signals Want Two Different Chips

Silver nanowires are a near-ideal plasmonic building block: high aspect ratio, strong tunable localized surface plasmon resonance, and — piled into a 3D mesh — a dense field of hot spots at every wire crossing plus an antenna effect that channels light along the wires. The engineering question the NanoSE work kept returning to is how to arrange those nanowires so the same structure simultaneously drives strong SERS (for fingerprint identity) and strong PEF (for bright, quantitative signal), reproducibly, from microliter volumes, on a solid chip a clinician or inspector could actually handle. Each of the three papers below is a more demanding version of that question — and a more capable answer.

The Platform, Explained

The common thread is a 3D silver-nanowire nanostructure read out two ways at once. Shine the laser, and molecules sitting in the hot spots give up a SERS fingerprint; fluorophores near the metal surface have their emission amplified by PEF, often by more than a thousandfold. One chip, one measurement, two orthogonal answers — what the molecule is (SERS) and how much is there (PEF) — which is exactly the redundancy a real diagnostic wants. The NanoSE line is the productized form of that dual-readout capability.

The Arc — One Platform, Three Generations

Before the 3D chips, the underlying physics was proven on our own bench: an AIEE fluorogen coupled to silver nanowires produced up to a 300-fold brightness gain, and time-resolved photoluminescence confirmed the boost was genuine plasmon–fluorophore coupling rather than just more dye. That mechanistic proof — covered in full in our TCSPC case-study post — is why the later chips could trust fluorescence enhancement as a design principle.

Generation 1 (2021) — The 3D-RCW Woodpile, Where NanoSE Begins

The first chip stacked silver nanowires into a random crossed-wire “woodpile” (3D-RCW), turning every wire crossing into an antenna-rich hot spot. It delivered both a SERS fingerprint and plasmon-enhanced fluorescence — the latter boosted more than 1000× — from microliter volumes, proven on four pesticides (thiram, carbaryl, paraquat, fipronil). This is the proof-of-concept the whole line traces back to.

Generation 2 (2022) — The 3D-PHS Chip Goes Clinical

The architecture matured into a plasmonic hotspot-rich (3D-PHS) chip and took on a clinical target: direct bilirubin in human blood, label-free, at ~10 nM from just 10 µL of serum — the first time direct bilirubin had been read in a clinically relevant range this way. The stakes were sharp: the direct/total bilirubin ratio had just been tied to survival in COVID-19 pneumonia.

Generation 3 (2023) — A Multiscale Substrate for a Pathogen

The hotspot architecture scaled across multiple length scales and took on the hardest target yet — SARS-CoV-2 spike protein, detected at 10 nM across three excitation wavelengths (532, 633, 785 nm). This is the generation where both Protrustech and Nanovie appear on the byline: the platform had become a co-developed product, not just a collaboration.

Each generation has its own deep dive: read Generation 1 (the 3D-RCW woodpile), Generation 2 (clinical direct-bilirubin), and Generation 3 (SARS-CoV-2 detection) in full.

The Three Generations, Side by Side

Why This Is Our Story

Everywhere else on this site, our pitch is third-party: independent researchers chose our instruments, and that independence is the credibility. This cluster is the opposite kind of credibility — and arguably the stronger one for a buyer deciding whether we understand the problem, not just sell the box. Protrustech and Nanovie people are named authors on this platform. We didn’t measure someone else’s chip; we helped design, build, and validate one, across three years, from a pesticide proof-of-concept to a clinical assay to a pandemic pathogen. When we say we understand dual-readout plasmonic sensing, this is the receipt.

Where This Sits — the Biosensor Network

NanoSE is the dual-readout, biosensing branch of a wider silver-nanostructure effort on the same Raman platform. Where the low-cost electroless and dewetting SERS substrates are single-readout chips optimized for cost and fabrication, NanoSE optimizes for clinical answer-quality — two orthogonal signals (SERS identity + PEF quantitation) from one 3D silver-nanowire chip. Read as a network, the pattern is a platform climbing the stakes — environmental → clinical → infectious disease — while the core capability stays constant. Same instrument family, different design goal: a useful contrast for a reader choosing between a cheap SERS chip and a clinical dual-readout platform. Both sit in our SERS Substrates: A Raman Field Guide.

Featured Solution:

Why This Matters

Dual-readout matters because real diagnostics can’t afford a single point of failure. A SERS fingerprint says what; a PEF signal says how much, brightly and fast. Getting both from one chip, from a 10 µL sample, on a benchtop Raman system, is the difference between a lab curiosity and a deployable point-of-care test — and the three-generation arc shows the same platform doing it for a food contaminant, a blood biomarker, and a virus. For a clinical, environmental, or public-health buyer, NanoSE is evidence that the dual-readout approach generalizes across exactly the range of targets they care about.

What’s Next

• Extending the multiscale-hotspot architecture to more clinical biomarkers and pathogens, building on the bilirubin and SARS-CoV-2 proofs.
• Pushing toward true point-of-care form factors — pairing the chips with portable Raman readers for field and bedside use.
• Formalizing the dual-readout calibration so SERS-identity and PEF-quantitation cross-check each other automatically in a single measurement.

Working on a biosensing problem where you need both molecular identity and quantitation from a tiny sample? This is the platform we co-developed for exactly that. Get in touch with our team.

Key Takeaways

• NanoSE is a dual-readout plasmonic biosensor platform — one 3D silver-nanowire chip gives both a SERS fingerprint (identity) and plasmon-enhanced fluorescence (bright quantitation) from microliter samples.
• It’s co-developed by our own team — Protrustech and Nanovie staff are named co-authors, the strongest signal on this site that we understand the sensing problem, not just supply the instrument.
• The platform climbs the stakes across three generations: pesticides (2021, >1000× PEF), clinical direct-bilirubin (2022, ~10 nM from 10 µL serum), and SARS-CoV-2 spike protein (2023, 10 nM across three lasers).
• The 2016 fluorescence-enhancement work is the physics forerunner — a 300× plasmon-fluorophore boost proven by TCSPC — that made the later chips’ design trustworthy.
• NanoSE is the dual-readout, clinical branch of the site’s silver-nanostructure work, distinct from the single-readout, low-cost SERS substrates (dewetting, electroless).

Featured Publications: