Distance-based detection (DbD) on paper-based microfluidic analytical devices (μPADs) has emerged as a promising, cost-effective, simple, and instrumentation-free assay method. Broadening the applicability of a new way of immobilization of reagent for DbD on μPADs (DμPADs) is presented, employing an ion exchange (IE) interaction of an anionic metallochromic reagent, 2-(5-bromo-2-pyridylazo)-5-[N-n-propyl-N-(3-sulfopropyl)amino]phenol (5-Br-PAPS), on the anion-exchange filter paper. The IE DμPADs demonstrate superiority over standard cellulose filter paper in terms of the degree of reagent immobilization, detection sensitivity, and clear detection endpoints due to the strong retention of 5-Br-PAPS. The study investigated various parameters influencing DbD, including 5-Br-PAPS concentrations (0.25-1 mM), buffer types (acetic acid-Tris, MES), buffer concentrations (20-500 mM), and auxiliary complexing agents (acetic, formic, and glycolic acids). Subsequently, the performance of 17 metals (Ag+, Cd2+, Co2+, Cr3+, Cu2+, Fe2+, Hg2+, La2+, Mn2+, Ni2+, Pb2+, Ti2+, Zn2+, Al3+, As3+, Fe3+, and V4+) was evaluated, with color formation observed for 12 metals. Additionally, the paper surface was examined using SEM and SEM-EDX to verify the suitability of certain areas in the detection channel for reagent immobilization and metal binding. This method demonstrates quantitation limits of metals in the low μg mL-1 range, showing great potential for the rapid screening of toxic metals commonly found in herbal supplements and cosmetics regulated by the Food and Drug Administration (FDA). Thus, it holds promise for enhancing safety and regulatory compliance in product quality assessment. Furthermore, this method offers a cost-effective, environmentally sustainable, and user-friendly approach for the rapid visual quantification of heavy metals for in-field analysis, eliminating the need for complex instrumentation.

Central European Institute of Technology Brno University of Technology Purkynova 123 CZ 612 00 Brno Czech Republic

Department of Chemistry and Biochemistry Mendel University in Brno Zemedelska 1 CZ 613 00 Brno Czech Republic

Department of Pharmaceutical Chemistry Faculty of Pharmacy Mahidol University 447 Sri Ayudhaya Rd Rajathevee Bangkok 10400 Thailand

School of Natural Sciences and Australian Centre for Research on Separation Science University of Tasmania Private Bag 75 Hobart 7001 Australia

See more in PubMed

Briffa J. Sinagra E. Blundell R. Heliyon. 2020;6:e04691. doi: 10.1016/j.heliyon.2020.e04691. PubMed DOI PMC

Tchounwou P. B. Yedjou C. G. Patlolla A. K. Sutton D. J. Exper. Suppl. 2012;101:133–164. doi: 10.1007/978-3-7643-8340-4_6. PubMed DOI PMC

United States Pharmacopeial Convention, <233> Elemental Impurities – Procedures, in United States Pharmacopeia and National Formulary, United States Pharmacopeial Convention, Rockville, MD

U.S. EPA, Method 200.7: Determination of Metals and Trace Elements in Water and Wastes by Inductively Coupled Plasma-Atomic Emission Spectrometry, Revision 4.4, Cincinnati, OH, 1994, https://www.epa.gov/sites/default/files/2015-06/documents/epa-200.7.pdf

ISO 21392:2021-Measurement of traces of heavy metals in cosmetic finished products using ICP/MS technique, https://www.iso.org/standard/70854.html

Lin Y. Gritsenko D. Feng S. Teh Y. C. Lu X. Xu J. Biosens. Bioelectron. 2016;83:256–266. doi: 10.1016/j.bios.2016.04.061. PubMed DOI

Nuchtavorn N. Macka M. Anal. Chim. Acta. 2016;919:70–77. doi: 10.1016/j.aca.2016.03.018. PubMed DOI

Manmana Y. Chutvirasakul B. Suntornsuk L. Nuchtavorn N. Pharm. Sci. Asia. 2019;46:270–277. doi: 10.29090/psa.2019.04.018.0037. DOI

Khunkitchai N. Nuchtavorn N. Rypar T. Vlcnovska M. Nejdl L. Vaculovicova M. Macka M. Chem. Eng. J. 2022;428:132508. doi: 10.1016/j.cej.2021.132508. DOI

Gong X. Shao J. Guo S. Pan J. Fan X. J. Pharm. Anal. 2021;11:603–610. doi: 10.1016/j.jpha.2020.09.004. PubMed DOI PMC

Nuchtavorn N. Leanpolchareanchai J. Suntornsuk L. Macka M. Anal. Chim. Acta. 2020;1098:86–93. doi: 10.1016/j.aca.2019.11.031. PubMed DOI

Vodova M. Nejdl L. Pavelicova K. Zemankova K. Rrypar T. Skopalova Sterbova D. Bezdekova J. Nuchtavorn N. Macka M. Adam V. Vaculovicova M. Food Chem. 2022;380:132141. doi: 10.1016/j.foodchem.2022.132141. PubMed DOI

Shen L. L. Zhang G. R. Etzold B. J. M. ChemElectroChem. 2020;7:10–30. doi: 10.1002/celc.201901495. PubMed DOI PMC

Zhang Y. Qian L. Yu Z. Yu Y. Feng C. Niu L. Zhang J. Microchem. J. 2024;196:109652. doi: 10.1016/j.microc.2023.109652. DOI

Al-Jaf S. H. Mohammed Ameen S. S. Omer K. M. Lab Chip. 2024;24:2306–2316. doi: 10.1039/D3LC01045G. PubMed DOI

Mesquita R. B. R. Klima C. Martínez-Pérez-Cejuela H. Monforte A. R. Ferreira A. C. S. Rangel A. O. S. S. Microchem. J. 2023;188:108462. doi: 10.1016/j.microc.2023.108462. DOI

Aryal P. Brack E. Alexander T. Henry C. S. Anal. Chem. 2023;95:5820–5827. doi: 10.1021/acs.analchem.3c00378. PubMed DOI

Jin B. Li Z. Zhao G. Ji J. Chen J. Yang Y. Xu R. Anal. Chim. Acta. 2022;1192:339388. doi: 10.1016/j.aca.2021.339388. PubMed DOI

Silva R. Ahamed A. Cheong Y. H. Zhao K. Ding R. Lisak G. Anal. Chim. Acta. 2022;1197:339495. doi: 10.1016/j.aca.2022.339495. PubMed DOI

Abdollahiyan P. Hasanzadeh M. Seidi F. Pashazadeh-Panahi P. J. Environ. Chem. Eng. 2021;9:106197. doi: 10.1016/j.jece.2021.106197. DOI

Miao Q. Qi J. Li Y. Fan X. Deng D. Yan X. He H. Luo L. Analyst. 2021;146:6297–6305. doi: 10.1039/D1AN01268A. PubMed DOI

Zhu L. Lv X. Li Z. Shi H. Zhang Y. Zhang L. Yu J. Biosens. Bioelectron. 2021;192:113524. doi: 10.1016/j.bios.2021.113524. PubMed DOI

Kamnoet P. Aeungmaitrepirom W. Menger R. F. Henry C. S. Analyst. 2021;146:2229–2239. doi: 10.1039/D0AN02200D. PubMed DOI PMC

Wang M. Song Z. Jiang Y. Zhang X. Wang L. Zhao H. Cui Y. Gu F. Wang Y. Zheng G. Anal. Bioanal. Chem. 2021;413:3299–3313. doi: 10.1007/s00216-021-03269-9. PubMed DOI

Zhang Y. Li Y.-L. Cui S.-H. Wen C.-Y. Li P. Yu J.-F. Tang S.-M. Zeng J.-B. J. Anal. Test. 2021;5:11–18. doi: 10.1007/s41664-021-00157-0. DOI

Zhou J. Li B. Qi A. Shi Y. Qi J. Xu H. Chen L. Sens. Actuators, B. 2020;305:127462. doi: 10.1016/j.snb.2019.127462. DOI

Xiong X. Zhang J. Wang Z. Liu C. Xiao W. Han J. Shi Q. BioChip J. 2020;14:429–437. doi: 10.1007/s13206-020-4407-9. PubMed DOI PMC

Guan Y. Sun B. Microsyst. Nanoeng. 2020;6:14. doi: 10.1038/s41378-019-0123-9. PubMed DOI PMC

Devadhasan J. P. Kim J. Sens. Actuators, B. 2018;273:18–24. doi: 10.1016/j.snb.2018.06.005. DOI

Hofstetter J. C. Wydallis J. B. Neymark G. Reilly Iii T. H. Harrington J. Henry C. S. Analyst. 2018;143:3085–3090. doi: 10.1039/C8AN00632F. PubMed DOI

Cai L. Fang Y. Mo Y. Huang Y. Xu C. Zhang Z. Wang M. AIP Adv. 2017;7:085214. doi: 10.1063/1.4999784. DOI

Cate D. M. Noblitt S. D. Volckens J. Henry C. S. Lab Chip. 2015;15:2808–2818. doi: 10.1039/C5LC00364D. PubMed DOI PMC

Chutvirasakul B. Nuchtavorn N. Macka M. Suntornsuk L. Anal. Bioanal. Chem. 2020;412:3221–3230. doi: 10.1007/s00216-020-02583-y. PubMed DOI

Chutvirasakul B. Nuchtavorn N. Suntornsuk L. Zeng Y. Electrophoresis. 2020;41:311–318. doi: 10.1002/elps.201900323. PubMed DOI

Nuchtavorn N. Rypar T. Nejdl L. Vaculovicova M. Macka M. Trends Anal. Chem. 2022;150:116581. doi: 10.1016/j.trac.2022.116581. DOI

Rahbar M. Wheeler A. R. Paull B. Macka M. Anal. Chem. 2019;91:8756–8761. doi: 10.1021/acs.analchem.9b01288. PubMed DOI

Pena-Pereira F. Wojnowski W. Tobiszewski M. Anal. Chem. 2020;92:10076–10082. doi: 10.1021/acs.analchem.0c01887. PubMed DOI PMC

Millero F. J. Feistel R. Wright D. G. McDougall T. J. Deep Sea Res., Part I. 2008;55:50–72. doi: 10.1016/j.dsr.2007.10.001. DOI

Bendre A. Bhat M. P. Lee K.-H. Altalhi T. Alruqi M. A. Kurkuri M. Mater. Today Adv. 2022;13:100205. doi: 10.1016/j.mtadv.2022.100205. DOI

AOAC, Guidelines for Dietary Supplements and Botanicals, 2019

Kuang Lu Cheng K. U., Imamura T., CRC Handbook of Organic Analytical Reagents, CRC Press, 2019

Yamada K. Henares T. G. Suzuki K. Citterio D. ACS Appl. Mater. Interfaces. 2015;7:24864–24875. doi: 10.1021/acsami.5b08124. PubMed DOI

Horiguchi D. Saito M. Noda K. Kina K. y. Anal. Sci. 1985;1:461–465. doi: 10.2116/analsci.1.461. DOI

Motomizu S. Oshima M. Kuwabara M. Obata Y. Analyst. 1994;119:1787–1792. doi: 10.1039/AN9941901787. DOI

Deng G. Collins G. E. J. Chromatogr. A. 2003;989:311–316. doi: 10.1016/S0021-9673(03)00080-3. PubMed DOI

Brown P. L. and Ekberg C., Hydrolysis of Metal Ions—Theory, Wiley-VCH Verlag GmbH & Co. KGaA, 2016

Skoog D. A., West D. M., Crouch S. R. and Holler F. J., Fundamentals of Analytical Chemistry, Brooks/Cole, Cengage Learning, 2014

Raj A. Rego R. M. Ajeya K. V. Jung H.-Y. Altalhi T. Neelgund G. M. Kigga M. Kurkuri M. D. Chem. Eng. J. 2023;453:139757. doi: 10.1016/j.cej.2022.139757. DOI

Rypar T. Adam V. Vaculovicova M. Macka M. Sens. Actuators, B. 2021;341:129999. doi: 10.1016/j.snb.2021.129999. DOI