MasSpec Pen Enables Noninvasive Opioid Detection

Opioids like fentanyl, morphine and oxycodone are the drugs most linked to overdoses in the US. Typical screening methods for drug usage involve collection of blood, saliva or urine samples. Now, in ACS’ Analytical Chemistry, researchers demonstrate a pen-like tool that can quickly and non-invasively collect molecules from the skin’s surface to be screened for opioids with mass spectrometry.

A common analytical method for detecting opioids in blood, saliva and urine samples is liquid chromatography mass spectrometry (LC-MS). Clinic-based LC-MS screening offers excellent detection and sensitivity, but sample collection and preparation is complicated and time-consuming. In addition to body fluids, opioids are also distributed in the skin. So, William Clarke, Livia Eberlin and colleagues came together to modify their handheld MasSpec Pen into a modular tool that quickly collects molecules from the skin’s surface to be tested for opioids, eliminating the need for additional sample prep.

The new version of the MasSpec Pen delivers a small droplet of water and ethanol to the surface of the skin. While it sits there, the liquid extracts molecules that could indicate past drug use. After 3 seconds, the liquid droplet is sucked up by the pen into a collection vial. The sample can be immediately analyzed by electrospray ionization mass spectrometry or stored for future analysis.

After successful proof-of-concept demonstrations on patches of human skin, the team tested the MasSpec Pen on the arm or hand of eight participants with known exposure to fentanyl and hydromorphone. When the researchers compared the new collection tool’s skin sample data to traditionally collected urine and saliva data, they found:

• Fentanyl in seven of the MasSpec Pen skin samples but no hydromorphone
• Fentanyl and hydromorphone in all eight urine samples 
• Fentanyl in five saliva samples (one sample could not be tested) and hydromorphone in four saliva samples.

Although the samples collected by the MasSpec Pen did not have the same level of detection as the urine and saliva samples, the device’s easy use and portability show promise for future development. The researchers note that discrepancies might stem from the time of drug ingestion relative to when the testing was performed. The team’s future studies may explore the impact of skin type, skin cleanliness and extent of drug exposure on the MasSpec Pen detection limits and analysis of opioids.

The authors acknowledge funding from the Eli Lilly Young Investigator Award, a Welch Research Grant and Thermo Fisher Scientific. The human skin samples used in this work were collected per the approved protocol from the Cooperative Human Tissue Network Institutional Review Board. The clinical study was conducted per the approved protocol from the Johns Hopkins University School of Medicine.

Some authors have patents on the MasSpec Pen and are involved in MS Pen Technologies, Inc., a company commercializing the technology. 

Reference: Gatmaitan AN, Weaver K, Badal SP, et al. Development and application of the modular MasSpec Pen system for clinical opioid screening. Anal Chem. 2025;97(21):11135-11144. doi: 10.1021/acs.analchem.5c00558

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