Sugar-Based Sensors Could Detect Snake Venom in Minutes

A new approach to detecting snake venom uses synthetic sugar molecules instead of expensive antibodies, potentially offering faster and cheaper diagnosis for bite victims.

Researchers at the University of Warwick have developed the first proof-of-concept test that uses glycopolymers—synthetic sugar chains—attached to gold nanoparticles to identify Western Diamondback Rattlesnake venom within 20 minutes. The color-changing test could help medical teams quickly determine which antivenom to administer in life-threatening situations.

Every five minutes, 50 people worldwide suffer snake bites, with four facing permanent disability and one death. Current diagnostic methods rely heavily on antibody-based tests that are costly, time-consuming, and often inconsistent in results.

Mimicking Nature’s Sugar Targets

Snake venoms have evolved to bind specific sugar molecules on human cell surfaces, including red blood cells and platelets. The Western Diamondback Rattlesnake’s venom specifically targets galactose-terminal glycans—sugar chains ending in galactose—which allows the toxins to disrupt blood clotting and interfere with immune responses.

The research team engineered synthetic versions of these natural sugar receptors using glycopolymers, then attached them to gold nanoparticles. When venom toxins bind to these synthetic sugars, the nanoparticles aggregate and produce a visible color change from red to blue or purple.

“Snake venoms are complex and detecting the toxins at work is challenging but essential to save lives,” said Dr. Alex Baker, Assistant Professor at Warwick and senior author of the study. “We’ve produced an assay using synthetic sugars that mimic the sugars in our bodies that the toxins naturally bind to and an amplification system that makes this rapid test visible.”

Key Test Performance Metrics:

• Detection limit of approximately 20 μg/mL for Western Diamondback venom
• Results visible within 20 minutes at room temperature
• Successfully distinguished between different snake species’ venoms
• No cross-reactivity with Indian Cobra venom, which lacks sugar-binding lectins

Beyond Simple Sugar Recognition

The researchers created a library of 19 different glycopolymer-functionalized gold nanoparticles, varying the sugar types, polymer chain lengths, and nanoparticle sizes. This systematic approach revealed crucial design principles that weren’t apparent from initial testing.

Most significantly, the study discovered that polymer chain length dramatically affects test stability and performance. The team found that longer polymer chains (52 units) successfully stabilized larger gold nanoparticles, while shorter chains (42 units) caused unwanted aggregation that would produce false positive results.

A critical finding overlooked in most diagnostic development: the researchers demonstrated that lactose-terminated systems required careful optimization of both polymer length and nanoparticle size to remain stable. Systems with 42-unit polymer chains attached to 40-nanometer particles aggregated spontaneously, while the same polymer worked perfectly with 16-nanometer particles. This sensitivity to multiple design parameters highlights the precision engineering required for reliable diagnostic tools.

Species-Specific Detection Capabilities

The sugar-based approach showed remarkable selectivity between different snake families. Tests with Indian Cobra venom, which belongs to the Elapidae family and lacks the lectin proteins found in Viperidae venoms like rattlesnakes, produced no detectable signal.

“This assay could be a real game-changer for snake envenomation,” noted Mahdi Hezwani, the study’s first author. “Venoms from other snake species do not interact with glycans in the body. For example, when we tested venom from the Indian Cobra (Naja naja) we did not see binding to the synthetic glycans that bind to C.atrox venom.”

This specificity addresses a critical medical need. Using the wrong antivenom can be less effective and may cause serious complications, while polyvalent antivenoms that work against multiple species carry higher risks of adverse side effects.

Comparing Detection Methods

The new test’s detection limit of 20 μg/mL compares favorably to some existing approaches. Previous latex agglutination tests for Crotalus species venoms achieved detection limits of 167 μg/mL with 10-minute assay times. However, the most sensitive antibody-based ELISA tests can detect nanogram-per-milliliter concentrations.

Pharmacokinetic studies suggest clinically relevant venom concentrations range from 1 to 1,000 ng/mL up to 50 hours after viper bites. While the current sugar-based test falls above this range, the researchers note that further refinement of polymer design, sugar selection, and nanoparticle optimization could significantly improve sensitivity.

Advantages Over Antibody Tests

Unlike antibody-based diagnostics, synthetic sugars don’t require animal immunization or cell culture production. They can be chemically synthesized with precise control over structure and function, potentially reducing costs and improving consistency.

The modular design allows researchers to customize sugar recognition elements for different snake species based on their known binding preferences. The same gold nanoparticle platform could accommodate various sugar types to create panels detecting multiple venom types.

Storage advantages also favor the synthetic approach. Antibodies typically require cold storage and have limited shelf lives, while synthetic glycopolymers should prove more stable under field conditions where snake bites often occur.

Future Applications and Development

The research builds on the Warwick team’s previous work using similar glyconanoparticle platforms for COVID-19 detection, demonstrating the versatility of the sugar-based diagnostic approach.

For snake envenomation, the next steps involve expanding the test to detect additional species, particularly those responsible for the highest global burden of bites. Different snake families and even species within families may require distinct sugar recognition elements based on their unique lectin profiles.

The WHO estimates snake envenomation causes approximately 100,000 deaths annually and three times as many permanent disabilities—figures believed to underestimate the true burden due to inadequate reporting systems. Improved diagnostic tools could help address this neglected tropical disease by enabling more precise treatment selection and better epidemiological tracking.

As Dr. Baker noted, this sugar-based detection method “lays the foundations for the rapid and cheap detection of snakebite beyond antibody-based techniques, potentially improving patient outcomes” in the critical hours following envenomation.