(Invited) Norfentanyl Detection with Carbon Nanotube-Based Field-Effect Transistors
Authors: Star Alexander 
Published: August 2024

The opioid crisis, propelled predominantly by synthetic opioids such as illicit fentanyl, constitutes a significant global public health threat. To meet the critical demand for a sensitive and portable analytical tool for detecting fentanyl exposure, we have developed two types of biosensors based on single-walled carbon nanotubes (SWCNTs).
The first biosensor is a field-effect transistor (FET) device with semiconductor-enriched SWCNTs, functionalized with norfentanyl antibody.1 This antibody-SWCNT-FET biosensor exhibits ultrasensitive detection of norfentanyl, the primary inactive metabolite of fentanyl, in urine samples. Various sensor configurations were investigated to optimize sensing results. The use of a "reduced" antibody facilitated oriented immobilization, enhancing the proximity of the antigen-antibody interaction to the sensor surface and resulting in improved sensitivity. These norfentanyl biosensors demonstrate remarkable sensitivity, with a limit of detection in the fg/mL range in both calibration and synthetic urine samples, showcasing their potential as highly reliable detection tools.
While capture probes like antibodies enhance chemical sensitivity and selectivity, the stability of nanotube-based biosensors is constrained by the activity of these capture probes. To address this limitation, we have explored an alternative approach involving sensor arrays consisting of different metal-organic frameworks (MOFs) on SWCNTs, which act as nonspecific receptors. With the assistance of machine learning-driven discrimination, such sensor arrays hold the potential to generate unique signals for different analytes.
In pursuit of this objective, size-based norfentanyl detection was achieved using SWCNT@MOF composites in FET biosensors.2 Four SWCNT@MOF composites were synthesized, with SWCNT@UiO-67 demonstrating the highest sensing response to norfentanyl due to a size-matching effect within the MOF channel. Composites with smaller pore sizes such as SWCNT@UiO-66 and SWCNT@UiO-66-NH2 did not exhibit sensitivity improvement compared to bare SWCNT. We have also demonstrated selectivity of these biosensors for norfentanyl over norhydrocodone and benzoylecgonine, which are major metabolites of hydrocodone and cocaine, respectively.
Moreover, we successfully applied our sensor fabrication with a flexible FET electrode and a portable sensing setup, showing significant potential for developing a portable device for on-site detection of fentanyl exposure with improved sensitivity. Therefore, we envision our norfentanyl biosensors can enhance the safety and security of both first responders and overdose victims and provide a platform technology that can contribute to the development of effective tools for addressing the opioid crisis.
[1] Shao, W.; Zeng, Z.; Star A., An Ultrasensitive Norfentanyl Sensor Based on a Carbon Nanotube-Based Field-Effect Transistor for the Detection of Fentanyl Exposure. ACS Appl. Mater. Interfaces
2023, 15, 37784–37793.
[2] Zeng, Z.; Islamov, M.; He, Y.; Day, B. A.; Rosi, N. L.; Wilmer, C. E.; Star, A., Size-Based Norfentanyl Detection with SWCNT @ UiO-MOF Composites. ACS Appl. Mater. Interfaces
2023, accepted.