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A new pilot rapid test for syphilis from a team led by Penn State researchers integrates two blood tests into one and detects bacteria at very low levels to detect the disease in its earliest stages. Credit: Pan Research Lab

Gold and Silver Particle Sharpens Rapid Syphilis Test Signals

In A Nutshell

  • Layered gold-silver-gold particles made rapid syphilis test lines 19% to 46% stronger than ordinary gold particles in lab tests.
  • Strips with the new particles picked up low-level samples that standard gold strips failed to show.
  • Results matched standard laboratory tests in all 36 clinical serum samples.
  • Fingerstick testing and clinic trials are still ahead, so the gain remains a lab result.

A modern rapid syphilis test can miss an infection when antibody levels in the blood run low, but a new particle built from layers of gold, silver, and gold may close that gap. In laboratory tests on clinical blood samples, strips carrying the layered particles produced test lines 19% to 46% stronger than strips with ordinary gold particles, and picked up low-level samples that the gold strips failed to show, according to a study in ACS Sensors.

Faint antibody signals matter most in early infection and during pregnancy, when untreated syphilis is linked to stillbirth, premature birth, and passing the infection to the baby. Cases, especially in newborns, have climbed sharply over the past decade, according to the paper. Rapid strips are meant to give an answer in a single visit, since sending samples to a lab adds delays, and some patients are lost before follow-up.

Researchers at Penn State and Louisiana State University set out to brighten that signal without making the particles too big to travel through the strip. Their strips develop in about 10 minutes, and the lines can be read by eye.

Plain Gold Particles Leave a Rapid Syphilis Test Too Faint

Rapid syphilis strips work much like a home pregnancy test. A sample creeps along a paper-like strip, and antibodies in it latch onto tiny gold particles, which pile up at a test line and turn it dark. This strip has two lines. One flags antibodies that usually stay detectable for life after infection, while the other tracks antibodies that fade after successful treatment, helping tell active infection from past infection.

Today, confirming syphilis usually takes a chain of lab tests. Rapid options exist, but the paper notes that some check for only one kind of antibody, and others lose sensitivity when antibody levels are low. Plain gold particles are part of the reason. With few antibodies around, too few particles reach a line to make it visible.

Bigger particles give a stronger color, but past roughly 60 nanometers, or 60 billionths of a meter, they struggle to squeeze through the strip’s fibers. For scale, a typical human hair is more than 1,000 times wider. Gold particles are stuck with a trade-off: small enough to travel, but too faint when antibodies are scarce.

nanoparticle syphilis test
The team used a variety of imaging techniques to capture the nanoparticle, including transmission electron microscopy (TEM), a technique that sends a beam of electrons through a sample. Here, the TEM images in the middle and right, which show the gold layers and silver layer, respectively, combine to form the composite image of the nanoparticle on the left. Credit: Pan Research Group

A Silver Middle Layer Makes Gold Particles Easier to See

Researchers started with a gold particle, wrapped it in a thin layer of silver, then added an outer shell of gold. Microscope images confirmed the silver sits between the two gold layers, like the filling in a sandwich, and the finished particles stayed small enough to travel.

Silver reacts to light far more strongly than gold, but it tarnishes easily and is harder to attach antibodies to. The gold coating shields it and keeps the particles stable in liquid. Computer simulations of an idealized version showed up to 18 times more light absorption than gold particles of the same size. In lab tests, a visible spot on the strip material needed about six times fewer layered particles than plain gold ones, and the layered spot came out a deeper, brownish red than gold’s plain red.

With a stand-in protein, layered particles also detected one-third as much material as plain gold could, a threefold gain. The gold comparison particles were nearly the same size, so researchers credit the gains mainly to the layering, not to bulk.

Syphilis Test Strips Matched Lab Results in 36 Samples

Next came clinical samples. Researchers tested 36 de-identified serum samples, the liquid part of blood, supplied by the CDC and a commercial supplier, Boca Biolistics. Most came from people with confirmed syphilis, a few from healthy controls, and antibody levels ranged from very low to very high.

Results matched standard laboratory tests in every sample, and the biggest gains showed up on the faintest ones.

Four samples carried only the lifelong antibodies, and the strip showed a signal on just that line, a hint that the two-line design can separate past or treated infection from active disease. Two HIV samples and two hepatitis C samples produced no false lines, though four samples is a small set for ruling out false alarms from other infections.

Fingerstick testing remains a goal, not a result. Every sample was serum, so the version that works from a finger prick, with plasma separated right on the strip, is still future work, along with testing in more places and more varied groups. If it pans out, strips like these could let clinics test and treat in the same visit, especially where lab access is limited. Using fewer particles could eventually lower costs, but the paper reports no cost figures. The authors describe the layering as a general design approach that could apply to other rapid tests.

A rapid test earns its speed only if it catches the infections that are hardest to see, and gold strips struggled with exactly those. Layered particles brought faint samples into view in the lab. Until clinic trials confirm it, the gain remains a lab result, not a proven one.


Disclaimer: This article reports on a single laboratory study and is for informational purposes only. It is not medical advice and does not recommend any test or treatment. The test described was evaluated only in the lab. Anyone concerned about syphilis or another infection should talk with a qualified health care professional.


Paper Notes

Limitations

Researchers used a small panel, 36 de-identified serum samples from two sources, with no demographic details reported. The paper’s text and Table 1 count the samples differently (the text lists 32 syphilis-positive samples and 4 healthy controls, while the table lists 28 treponemal-reactive and 8 nonreactive samples), and the table’s CDC non-treponemal counts add up to 17 for a group of 15. The 18-fold absorption figure comes from simulations of an idealized particle, and the threefold detection gain came from a streptavidin model rather than syphilis antibodies. Specificity testing used two HIV and two hepatitis C samples, and the authors note that samples from co-infected patients still need testing to confirm positive signals are not suppressed. The fingerstick workflow with on-strip plasma separation was not tested. Comparisons used about 50-nanometer gold particles as the standard.

Funding and Disclosures

Funding came from the National Institutes of Health (National Institute of Allergy and Infectious Diseases award R01AI185115 and National Heart, Lung, and Blood Institute award R01HL173540, both to corresponding author Dipanjan Pan), the Centers for Disease Control and Prevention (award 75D30122C15492), the National Science Foundation (awards CBET 2153091 and 2229986), and the Department of Defense Congressionally Directed Medical Research Program (award TP210376). Co-author Manas Ranjan Gartia was supported by the National Institute of General Medical Sciences (award R35GM150564). The authors declare a competing financial interest: Penn State filed a pending international patent application (PCT/US2025/052770, “Platform for Direct Treponemal and Nontreponemal Lateral Flow Assay for Syphilis”) on behalf of Pan, Ketan Dighe, and Satheesh Natarajan. Pan also founded or co-founded three university-based startups, none of which supported this work.

Publication Details

This report covers the study “Multilayer Plasmon Hybridization in Au-Ag-Au Nanoparticles Enables Extinction Amplification in Transport-Limited One-Step Confirmatory Syphilis Biosensing,” which appears in ACS Sensors, published by the American Chemical Society as an open-access article under a CC-BY 4.0 license. Authors are Ketan Dighe, Satheesh Natarajan, Maria Iftesum, Shraddha Krishnakumar, David Skrodzki, Matthew Molinaro, Nivetha Gunaseelan, Casey N. Pinto, Manas Ranjan Gartia, and Dipanjan Pan (corresponding author, Pennsylvania State University, [email protected]). Co-authors are affiliated with Pennsylvania State University, Penn State College of Medicine, and Louisiana State University. The paper was received June 8, 2026, revised August 7, 2026, and accepted August 10, 2026. Volume, issue, and page numbers were not yet assigned in the reviewed version. DOI: 10.1021/acssensors.6c02500 (https://doi.org/10.1021/acssensors.6c02500).

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