Fabrication of Paper-Based Electrochemical Devices and Detection of Acetaminophen
Authors: Chung Woo Sung , Lee Sung Hwan , Lee Joo Heon , Tran Van-Khue , Ko Euna , Park Chan Ho , Seong Gi Hun 
Published: February 2020

Compact diagnostic devices, known as point-of-care devices, are receiving more interest due to their advantages of instant use, portability and vast applicability. The main value of point-of-care devices is health awareness and capability of self-diagnosis for individuals. Currently, according to the market’s need for appropriate remedies, more sensitive and selective devices are demanded. In that sense, paper-based diagnostic and analytical devices have attracted significant interest due to their low-cost, portability, simplicity and suitability of use in the field and developing countries. Here, the electrochemical sensing method was selected because of its agreement with markets’ need for paper-based analytical devices such as the ability of quantitative analysis, high sensitivity, fast sensor response and portability.

Acetaminophen (N-acetyl-p-aminophenol), known as paracetamol, is an antipyretic analgesic, commonly used for the relief of headaches, backache, arthritis and other incidental pains and fevers. When taken in therapeutic doses, acetaminophen is safe, non-carcinogenic and does not have the secondary effects of acetylsalicylic acid. Surprisingly, acetaminophen is also the most common cause of poisoning worldwide. Acetaminophen poisoning can be the result of a single overdose ingestion (usually as an attempt at self-harm) or ingestion of excessive repeated doses or too-frequent doses, with therapeutic intent. Although the normal concentration range of acetaminophen for therapeutic purposes may vary due to personal constitution and physique, the plasma concentration of acetaminophen in humans follows a standard drug dose ranging from 50 to 100 μM. Therefore, a simple and quick measurement of acetaminophen doses is necessary for a continuous or urgent diagnosis.

In the present study, we constructed a functional paper fluidic device and evaluated its electrochemical performance by analyzing acetaminophen in the presence of ascorbic acid. The device was composed of a single-walled carbon nanotube (SWCNT) electrode and nafion-modified nitrocellulose membrane. Negatively-charged nafion was employed to build up a more negative charge on the nitrocellulose membrane, and gold nanoparticles and polyglutamic acid (AuNP-PGA) were deposited on the SWCNT electrode to enhance the electrochemical performance of the device. The device had a vertical flow format in which the sample solution flowed vertically through the paper. Using the nafion-modified nitrocellulose membrane and AuNP-PGA/SWCNT film electrode as a component of the paper fluidic device, we obtained a distinguishable acetaminophen oxidation peak which was distinct from the ascorbic acid oxidation peak. The acetaminophen oxidation peak had a linear response with acetaminophen concentration, varying from 50 μM to 300 μM (r2 = 0.992), which was broader than the standard drug dose range. The device exhibited a sensitivity of 13.3 mA/M and a detection limit of 15.0 μM. The device was stable with a relative standard deviation of 3.3% (up to 2 weeks), and the reproducibility was 1.2 to 5.2%. Furthermore, the fabricated device accurately measured the amount of acetaminophen in pharmaceutical samples. From the results, we believe that the fabricated device is a promising electrochemical platform for the accurate and reproducible detection of acetaminophen and paper fluidic devices have the potential for simultaneous detection of multiple analytes with high selectivity by applying various materials such as enzymes, polymers, or aptamers on the membrane.