Elsevier

Sensors and Actuators B: Chemical

Volume 232, September 2016, Pages 514-522
Sensors and Actuators B: Chemical

Determination of acetaminophen using functional paper-based electrochemical devices

https://doi.org/10.1016/j.snb.2016.03.169Get rights and content

Abstract

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 1.2–5.2%. Furthermore, the fabricated device accurately measured the amount of acetaminophen in pharmaceutical samples.

Introduction

In June, 2015 in Geneva, the World Health Organization (WHO) re-emphasized the importance of diagnostics in global consultation and stated that diagnostics are critical for a successful delivery of healthcare. Furthermore, the WHO set helpful criteria for diagnostic devices, which are affordable by subjects at risk of infection, sensitive, specific, user-friendly, rapid and robust, equipment-free, and delivered to those who need it (abbreviated as ASSURED) [1]. Fortunately, there is a field of research pertaining to this subject. Starting with Whitesides group’s groundbreaking studies regarding patterned paper platforms [2], 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 [3], [4]. Due to large interest, many diverse end products have been developed resulting in widely available paper-based analytical devices for various applicationssuch as immunoassays [5], urinalysis [6], veterinary medicine [7], environmental monitoring [8], food safety [9], bioterrorism [10] and drug abuse [11]. In addition, the product robustness is satisfactory and the assays are rapid and simple. However, the majority of tests only providea yes or no answer to the user and often have lower specificity and sensitivity than laboratory bench tests. Therefore, major markets are demanding more sensitive and specific diagnostic assays while maintaining a low-cost [12].

Paper-based devices in analytical research fields have established assorted formats depending on their shape and use. Lateral flow is one of the most popular formats commonly used as biosensors. Utilizing capillary-based flow and various patterning techniques [13], [14], [15], lateral flow format enables fluid manipulation and lateral flow-based assays, hence achieving broad applicability [16], [17], [18]. The lateral flow format has advantages such as good selectivity, rapid parallel detection ability for multi-analytes, low quantity of sample volume requirement, elimination of the washing step, robustness and low cost. Conversely, lateral flow has drawbacks, such as a large sample volume requirement, when running multiplexed lateral flow tests, risk of contamination during the transportation or operation and evaporation of sample [19], [20]. Vertical format (flow-through) [21], [22] and three-dimensional format [23], [24], [25] are occasionally considered as a complex format; however, their potential is significant. While multiplexed diagnosis of lateral flow devices requires large sample volumes and co-optimization of the fluidic pathway to avoid interference or competition among designed assays, vertical and three-dimensional flow devices require small sample volume and interconnected layers and pathways without interference or competition [19], [23]. The advantages of vertical and three-dimensional flow formats are stackable layers; complex functionality can be allowed easily on vertical flow formats and fluid manipulability can be controlled by stacking layers without elongation of the fluid pathway, run-time and increment of sample consumption.

Acetaminophen (N-acetyl-p-aminophenol), also known as paracetamol, is an antipyretic analgesic, commonly used for the relief of headaches, backache, arthritis and other incidental pains and fevers [26], [27]. 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 [28], [29]. 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 [30]. 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 [31]. Therefore, a simple and quick measurement of acetaminophen doses is necessary for a continuous or urgent diagnosis.

In this study, we constructed paper-based diagnostic devices with nafion-modified nitrocellulose membrane for electrochemical detection of acetaminophen. For diagnostic assays, various analysis techniques, such as colorimetry, fluorescence, electrochemical sensing, chemiluminescence and surface-enhanced Raman spectroscopy, have been employed. 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. Micro-patterned single-wall carbon nanotube (SWCNT) film was used as the electrode, on which gold nanoparticle (AuNP) and polyglutamic acid (PGA) were electrochemically co-deposited. To test our device, we chose acetaminophen as the target analyte to quantify and chose ascorbic acid as the interfering agent. To block the oxidation of ascorbic acid on the electrode surface, the nitrocellulose membrane of our vertical flow devices was modified with negatively-charged nafion. Furthermore, the acetaminophen concentration of several pharmaceutical tablet preparations was determined to evaluate the performance of the device.

Section snippets

Materials

The SWCNT layer on polyethylene terephthalate (PET) film was obtained from Sangbo (Seoul, South Korea). Gold (III) chloride trihydrate, l-glutamic acid, acetaminophen, l-ascorbic acid and nafion were purchased from Sigma-Aldrich (St. Louis, MO, USA). Nitrocellulose membranes with 0.22 μm pore size were purchased from Merck Millipore (Darmstadt, Germany). The 20 × Phosphate buffered saline (PBS) solution was obtained from Biosesang (Seong Nam, South Korea). AZ 4620 photoresist and AZ 400 K developer

Results and discussion

Fig. 1 shows the schematic of the paper fluidic device. The three-patterned SWCNT electrodes had reliable reproducibility, with conformation of 700 μm width and 300 μm spacing between electrodes. The keyhole-shaped well was positioned above the electrode to form a small gap between electrode and nitrocellulose membrane. The keyhole-shaped well was designed to function as the sample solution reservoir where electrochemical analysis was performed. The nafion-modified nitrocellulose membrane was

Conclusion

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. To propose agreeable platforms for point-of-care devices and fulfil the needs, we fabricated a functional

Acknowledgements

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Science, ICT & Future Planning (2008-0061891 and 2013R1A1A2054887).

Sung Hwan Lee received the BS degree in department of material engineering, Hanyang University, South Korea in 2014. He is presently a MS student in department of bionano engineering, Hanyang University, South Korea. His current research interest is the development of electrochemical paper-based fluidic devices.

References (41)

  • W.H. Organization, Global Consultation on Diagnostics Interoperability Standards: 11–12 June 2015, Geneva, Switzerland,...
  • A.W. Martinez et al.

    Patterned paper as a platform for inexpensive low-volume, portable bioassays

    Angew. Chem. Int. Ed.

    (2007)
  • C. Zhao et al.

    A microfluidic paper-based electrochemical biosensor array for multiplexed detection of metabolic biomarkers

    Sci. Tech. Adv. Mater.

    (2013)
  • Z. Nie et al.

    Electrochemical sensing in paper-based microfluidic devices

    Lab Chip

    (2010)
  • Alere Inc. Home Page. http://www.alere.com (accessed...
  • Swiss Precision Diagnostics GmbH Home Page. http://www.swissprecisiondiagnostics.com (accessed...
  • Audit Diagnostics Home Page. http://www.auditdiagnostics.ie/products/veterinary (accessed...
  • Wagtech WTD, Palintest Ltd. Home Page. http://www.wagtech.co.uk (accessed...
  • Romer Labs, Inc. Home Page. http://www.romerlabs.com (accessed...
  • Southern Scientific Ltd. Home Page. http://www.southernscientific.co.uk (accessed...
  • Cited by (0)

    Sung Hwan Lee received the BS degree in department of material engineering, Hanyang University, South Korea in 2014. He is presently a MS student in department of bionano engineering, Hanyang University, South Korea. His current research interest is the development of electrochemical paper-based fluidic devices.

    Joo Heon Lee received the BS degree in department of bionano engineering, Hanyang University, South Korea in 2014. He is presently a MS student in department of bionano engineering, Hanyang University, South Korea. His current research interest is the development of electrochemical biosensor based on nanomaterials.

    Van-Khue Tran received the BS degree in biochemistry from University of Science, Ho Chi Minh City, Viet Nam in 2009. He is presently a PhD student in department of bionano engineering, Hanyang University, South Korea. His research interest is the development of electrochemical paper-based fluidic devices.

    Euna Ko received the BS degree in applied chemistry from Hanyang University, South Korea in 2013. She is presently a PhD student in department of bionano engineering, Hanyang University, South Korea. Her current research interest is the development of electrochemical microfluidic devices.

    Chan Ho Park received the BS degree in applied chemistry from Hanyang University, South Korea in 2014. He is presently a MS student in department of bionano engineering, Hanyang University, South Korea. His current research interest is the development of electrochemical paper-based fluidic devices.Woo Sung Chung received the BS degree in department of bionano engineering, Hanyang University, South Korea in 2015. He is presently a MS student in department of bionano engineering, Hanyang University, South Korea. His current research interest is the development of electrochemical biosensor.

    Woo Sung Chung received the BS degree in department of bionano engineering, Hanyang University, South Korea in 2015. He is presently a MS student in department of bionano engineering, Hanyang University, South Korea. His current research interest is the development of electrochemical biosensor.

    Gi Hun Seong received the BS and MS degrees in chemical engineering from Korea Advanced Institute of Science and Technology (KAIST) in 1993 and 1995, respectively, and his PhD degree in bioscience and biotechnology from Tokyo Institute of Technology, Japan in 2001. He joined the chemistry department, Texas A&M University as a postdoctoral research fellow from 2001 to 2003. He is presently a professor in the department of bionano engineering, Hanyang University, South Korea. His research interests are nanomaterials-based bio/chemical sensors, electrochemical microbiochips, and nanoparticles fabrication.

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