title: Paper-based Microfluidic Electrochemical Sensor Devices With 3D Electrode Arrangement
Creators: name: Ghanbari, Mohammad Hossein
Publisher: name: Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
Year: 2025

description: The increasing demand in healthcare for affordable and accessible analytical tools is driving the advancement of reliable platforms. Screen-printed carbon-based electrodes are a common choice for use as portable sensors. However, paper-based microfluidic electrochemical sensors offer the additional benefits of high sensitivity, reliability and fast analysis. Microfluidic platforms based on paper offer new opportunities for advancements in various fields and miniaturization of diverse technologies within on-chip devices. Also, it opens up new possibilities for 3D arrangement of electrodes. This advancement aims to create a wide range of inexpensive products for everyday life. This dissertation studies how paper-based microfluidic electrochemical sensors can enhance the detection of both inorganic and organic analytes, with a particular focus on illustrative case studies for each category. A significant element of the research is an investigation of the influence of electrode arrangements on the overall performance of the sensor. Furthermore, the study examines how paper-based microfluidics can facilitate reaction processes, thereby enhancing efficiency and effectiveness. The role of electrocatalysts in influencing sensor functionality is examined, and direct electro-deposition and electro-polymerization techniques are evaluated for their potential to enhance performance in biological sensing applications. Scalable technology, such as screen printing, is employed to fabricate these devices in an efficient and cost-effective manner, thereby facilitating the potential for mass production of electrodes screen printed onto or into paper substrates. The feasibility of these sensors is further considered for applications in pharmacokinetic analysis and clinical testing, particularly in the context of personalizing treatment management for conditions like schizophrenia through the sensing of clozapine. The objective of this research is to enhance the sensitivity and functionality of the sensors while addressing the challenges associated with detecting diverse analytes by integrating innovative materials, fabrication, and design techniques. The research can be broken down in three connected subtopics, which were also published on separated articles: • A 3D paper-based microfluidic electrochemical sensor based on N-doped carbon nanoonions/nafion for detection of heavy metal ions when compared to screen-printed carbon-based electrodes. • Clozapine sensing through a 3D paper-based microfluidic electrochemical sensor directly modified via electro-deposition and electro-polymerization. • Screen printed 3D paper-based microfluidic and modifier-free electroanalytical device for clozapine sensing. The first study demonstrates the enhanced performance of the 3D paper-based microfluidic electrochemical sensor over screen-printed carbon-based electrodes for monitoring ultra-trace levels of Cd2+. The 3D paper-based microfluidic electrochemical sensor utilizes a microfluidic paper strip in conjunction with a 3D configuration, featuring three electrodes fabricated from pristine graphite foil. Furthermore, N-doped carbon nanoonions are presented as sustainable non-metallic modifier and used as an electrocatalyst for working electrode modification which increase the electron transfer rate and the electrochemically active surface area in both arrangements together with enhance sensitivity. Both arrangements were compared utilizing electrochemical impedance spectroscopy and cyclic voltammetry in [Fe(CN)6]3−/4− as a probe solution, also square wave voltammetry for Cd2+ detection. The 3D paper-based microfluidic electrochemical sensor clearly outperforms the screen-printed carbon-based electrodes in terms of signal strength. This cost-effective, straightforward, and portable sensor demonstrates remarkable sensitivity for detecting trace amounts of heavy metal ions in aqueous solutions, with a detection limit and sensitivity reaching to 0.25 μg L−1 and 1.02 μA µg-1 L cm-2 for Cd2+, respectively. In addition, this great sensitivity is combined with high stability, tested with 8 repetitive measurements with a single device, resulting in remarkable reproducibility. Furthermore, the sensor successfully detects Cd2+ ions in more complex environments, such as mineral water and river water samples. These findings highlight the device's exceptional potential of the device for the adsorption and detection of heavy metal ions. A further study was conducted to determine the sensor's ability to detect and determine organic compounds. The second study presents the novel approach of direct electro-deposition of gold nanoparticles and electro-polymerization of L-cysteine for the first time to modify the surface of the working electrode through a 3D paper-based microfluidic electrochemical sensor. This modification technique was shown to enhance the electrochemically active surface area and the electron transfer rate, thereby improving sensitivity. Modified and unmodified arrangements were compared employing electrochemical impedance spectroscopy and cyclic voltammetry in [Fe(CN)6]3−/4−, as well as square wave voltammetry for anti-psychotic medication clozapine sensing. The sensor depicts remarkable sensitivity for detecting trace amounts of clozapine in aqueous solutions, with a detection limit of 70.0 nM. Furthermore, the sensor is capable of detecting clozapine in more complex matrices like human blood serum samples. The 3D paper-based microfluidic electrochemical sensor provides a cost-effective, straightforward, and highly sensitive sensing platform, making it an ideal choice for point-of-care diagnostics. Following the successful application of the sensor in the detection and determination of clozapine as an organic sample, a decision was made to investigate the possibility of producing such devices by scalable technology like screen printing. This was considered a promising direction for further investigation. The third study presents a 3D microfluidic paper-based electroanalytical device fabricated by screen printing electrodes on/in both sides of paper to create a 3D electrode layout. The enhanced capabilities of the 3D electrode layout of microfluidic paper-based electroanalytical device compared to 2D microfluidic paper-based electroanalytical device arrangement in the context of clozapine sensing via square wave voltammetry in addition to study via cyclic voltammetry in [Fe(CN)6]3−/4−. The findings clearly suggest that the 3D electrode layout of the microfluidic paper-based electroanalytical device holds promise as an economical and effective sensing tool for point-of-care diagnostics through increasing the electrochemically active surface area which consequently improves the sensitivity for sensing. Under the optimized conditions, a linear dose-response for a concentration range of 7.0 to 100 μM was successfully achieved. The detection limit and sensitivity were determined to be 1.47 μM and 1.69 μA µM-1 cm-2, respectively. These findings highlight the potential of the 3D microfluidic paper-based electroanalytical device as a tool for future clinical trials, with the aim of personalizing the management of schizophrenia. This dissertation emphasizes that 3D microfluidic paper-based electroanalytical devices represent a promising approach for the creation of low-cost, environmentally friendly, portable, and user-friendly sensing platforms. The importance of fluid flow and the 3D electrodes arrangement in such devices is emphasized, illustrating their benefits for both inorganic and organic sensing applications. Moreover, the incorporation of appropriate electrocatalysts markedly enhances the efficacy of these platforms in real sample analysis. In addition to the design and fabrication of sophisticated 3D microfluidic paper-based electroanalytical devices, comprehensive studies are conducted to examine the impact of device structure, including electrode arrangement and working electrode modification, on overall performance. Furthermore, the advantages of these 3D microfluidic paper-based electroanalytical devices can be further enhanced through the implementation of scalable production techniques, such as screen printing, thereby facilitating their integration into a broader range of advanced sensing technologies. The findings of this research may prove valuable in guiding the development of future 3D microfluidic paper-based electroanalytical devices.