skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


This content will become publicly available on April 1, 2026

Title: A Supramolecular–Quantum Dot System for Broad‐Spectrum Detection of Fentanyl Analogs
Abstract Synthetic opioids, especially fentanyl and its analogs, have created an epidemic of abuse and significantly increased overdose deaths in the United States. Current detection methods have drawbacks in their sensitivity, scalability, and portability that limit field‐based application to promote public health and safety. The need to detect trace amounts of fentanyl in complex mixtures with other drugs or interferents, and the continued emergence of new fentanyl analogs, further complicates detection. Accordingly, there is an urgent need to develop convenient, rapid, and reliable sensors for fentanyl detection. In this study, a sensor is prepared based on competitive displacement of a fluorescent dye from the cavity of a supramolecular macrocycle, with subsequent fluorescence quenching from graphene quantum dots. This approach can detect and quantify small quantities of fentanyl along with 58 fentanyl analogs, including highly potent variants like carfentanil that are of increasing concern. Detection of these agents is possible even at 0.01 mol% in the presence of common interferents. This simple, rapid, reliable, sensitive, and cost‐effective approach couples supramolecular capture with graphene quantum dot nanomaterial quenchers to create a tool with the potential to advance public health and safety in the context of field‐based detection of drugs in the fentanyl class.  more » « less
Award ID(s):
2337387
PAR ID:
10586726
Author(s) / Creator(s):
; ; ; ; ; ; ;
Publisher / Repository:
Wiley
Date Published:
Journal Name:
Small
Volume:
21
Issue:
16
ISSN:
1613-6810
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract BackgroundFentanyl test strips (FTS) are a commonly deployed tool in drug checking, used to test for the presence of fentanyl in street drug samples prior to consumption. Previous reports indicate that in addition to fentanyl, FTS can also detect fentanyl analogs like acetyl fentanyl and butyryl fentanyl, with conflicting reports on their ability to detect fentanyl analogs like Carfentanil and furanyl fentanyl. Yet with hundreds of known fentanyl analogs, there has been no large-scale study rationalizing FTS reactivity to different fentanyl analogs. MethodsIn this study, 251 synthetic opioids—including 214 fentanyl analogs—were screened on two brands of fentanyl test strips to (1) assess the differences in the ability of two brands of fentanyl test strips to detect fentanyl-related compounds and (2) determine which moieties in fentanyl analog chemical structures are most crucial for FTS detection. Two FTS brands were assessed in this study: BTNX Rapid Response and WHPM DanceSafe. ResultsOf 251 screened compounds assessed, 121 compounds were detectable at or below 20,000 ng/mL by both BTNX and DanceSafe FTS, 50 were not detectable by either brand, and 80 were detectable by one brand but not the other (n = 52 BTNX,n = 28 DanceSafe). A structural analysis of fentanyl analogs screened revealed that in general, bulky modifications to the phenethyl moiety inhibit detection by BTNX FTS while bulky modifications to the carbonyl moiety inhibit detection by DanceSafe FTS. ConclusionsThe different “blind spots” are caused by different haptens used to elicit the antibodies for these different strips. By utilizing both brands of FTS in routine drug checking, users could increase the chances of detecting fentanyl analogs in the “blind spot” of one brand. 
    more » « less
  2. Abstract Background The opioid epidemic has caused an increase in overdose deaths which can be attributed to fentanyl combined with various illicit substances. Drug checking programs have been started by many harm reduction groups to provide tools for users to determine the composition of their street drugs. Immunoassay fentanyl test strips (FTS) allow users to test drugs for fentanyl by either filling a baggie or cooker with water to dissolve the sample and test. The antibody used in FTS is very selective for fentanyl at high dilutions, a characteristic of the traditional use of urine testing. These street sample preparation methods can lead to mg/mL concentrations of several potential interferents. We tested whether these concentrated samples could cause false positive results on a FTS. Methods 20 ng/mL Rapid Response FTS were obtained from BTNX Inc. and tested against 4 different pharmaceuticals (diphenhydramine, alprazolam, gabapentin, and naloxone buprenorphine) and 3 illicit stimulants [cocaine HCl, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA)] in concentrations from 20 to 0.2 mg/mL. The FTS testing pad is divided into 2 sections: the control area and the test area. Control and test area signal intensities were quantified by ImageJ from photographs of the test strips and compared to a threshold set by fentanyl at the FTS limit of detection. Results False positive results indicating the presence of fentanyl were obtained from samples of methamphetamine, MDMA, and diphenhydramine at concentrations at or above 1 mg/mL. Diphenhydramine is a common cutting agent in heroin. The street sample preparation protocols for FTS use suggested by many online resources would produce such concentrations of these materials. Street samples need to be diluted more significantly to avoid interference from potential cutting agents and stimulants. Conclusions Fentanyl test strips are commercially available, successful at detecting fentanyl to the specified limit of detection and can be a valuable tool for harm reduction efforts. Users should be aware that when drugs and adulterants are in high concentrations, FTS can give a false positive result. 
    more » « less
  3. Detection of illicit drug residues from wastewater provides a new route toward community-level assessment of drug abuse that is critical to public health. However, traditional chemistry analytical tools such as high-performance liquid chromatography in tandem with mass spectrometry (HPLC-MS) cannot meet the large-scale testing requirement in terms of cost, promptness, and convenience of use. In this article, we demonstrated ultra-sensitive and portable surface-enhanced Raman scattering sensing (SERS) of fentanyl, a synthetic opioid, from sewage water and achieved quantitative analysis through principal component analysis and partial least-squares regression. The SERS substrates adopted in this application were synthesized by in situ growth of silver nanoparticles on diatomaceous earth films, which show ultra-high sensitivity down to 10 parts per trillion in artificially contaminated tap water in the lab using a commercial portable Raman spectrometer. Based on training data from artificially contaminated tap water, we predicted the fentanyl concentration in the sewage water from a wastewater treatment plant to be 0.8 parts per billion (ppb). As a comparison, the HPLC-MS confirmed the fentanyl concentration was below 1 ppb but failed to provide a specific value of the concentration since the concentration was too low. In addition, we further proved the validity of our SERS sensing technique by comparing SERS results from multiple sewage water treatment plants, and the results are consistent with the public health data from our local health authority. Such SERS sensing technique with ultra-high sensitivity down to sub-ppb level proved its feasibility for point-of-care detection of illicit drugs from sewage water, which is crucial to assess public health. 
    more » « less
  4. Abstract Overdose deaths involving fentanyl represent a major public health crisis in the USA. This study investigates the spatiotemporal dynamics of fentanyl-involved deaths before, during, and after the COVID-19 pandemic and examines how sociodemographic factors influence these deaths across geographic regions. Using a retrospective ecological approach, we analyzed data on ZIP code-level fentanyl-related deaths in Cook County, IL, between 2018 and 2023, obtained from the Medical Examiner’s Office and linked with sociodemographic data from the American Community Survey. We first mapped area-level death rates to assess their distribution and then conducted global and local clustering analyses to identify spatial autocorrelations and the locations of high- or low-death-rate areas. A geographically weighted Poisson regression (GWPR) model evaluated the associations between area-level fentanyl-related death rates and the area-level proportion of young adults, males, and individuals with at least a college degree, disability rate, and poverty rate. Spatial analyses found stronger spatial autocorrelations during (2020–2021) and after (2022–2023) the pandemic. Initially, high death rates were concentrated in the downtown area of Chicago, and they expanded to the surrounding areas during and after the pandemic. The GWPR model revealed that an increase in the area-level proportions of poverty, disability, and young adult residents increased the fentanyl-related death rates in most of the areas. Our findings highlight the urgent need to address the evolving dynamics of fentanyl-related overdoses through tailored public health interventions that account for the unique socioeconomic determinants of different regions. Importantly, a comprehensive approach to addressing differences in overdose death rates and their risk factors will be crucial to mitigating this public health crisis. 
    more » « less
  5. Abstract Aptamers are nucleic acid bioreceptors that have been used in various applications including medical diagnostics and as therapeutic agents. Identifying the most optimal aptamer for a particular application is very challenging. Here, we for the first time have developed a high-throughput method for accurately quantifying aptamer binding affinity, specificity, and cross-reactivity via the kinetics of aptamer digestion by exonucleases. We demonstrate the utility of this approach by isolating a set of new aptamers for fentanyl and its analogs, and then characterizing the binding properties of 655 aptamer–ligand pairs using our exonuclease digestion assay and validating the results with gold-standard methodologies. These data were used to select optimal aptamers for the development of new sensors that detect fentanyl and its analogs in different analytical contexts. Our approach dramatically accelerates the aptamer characterization process and streamlines sensor development, and if coupled with robotics, could enable high-throughput quantitative analysis of thousands of aptamer–ligand pairs. 
    more » « less