Herein we report a quantitative, multiplex assay for disease markers in plasma based on an integrated setup of a portable scanner and a disposable paper-based analytical device (PAD). The quantitative analysis relies on the digital colorimetric reading of the three-layer PAD with 30 assay sites for performing respective chromogenic reactions for plasma uric acid, glucose, and triglyceride, which are considered as important risk factors for cardiovascular diseases. A portable scanner with WiFi transmission capability was used to produce high-quality color images of the PADs and wirelessly transfer them to a smartphone or other mobile devices for data processing. The concentrations of biomarkers in both standard solutions and plasma samples can be directly obtained using a custom-designed smartphone app that is also capable of constructing calibration curves. The detection limits of uric acid, glucose, and triglyceride were determined to be 0.50 mg/dL, 0.84 mmol/L, and 14 mg/dL, respectively, which are below the normal limits and adequate for clinical validation. Owing to the distinct advantages—simple, portable, and cost-effective—this mobile assay protocol can be used for point-of-care (POC) settings or resource-limited situations, and potentially for the diagnosis and prevention of infectious diseases.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Nahand JS, Taghizadeh-Boroujeni S, Karimzadeh M, Borran S, Pourhanifeh MH, Moghoofei M, et al. microRNAs: new prognostic, diagnostic, and therapeutic biomarkers in cervical cancer. J Cell Physiol. 2019;234(10):17064–99.
Perazella MA, Coca SG. Three feasible strategies to minimize kidney injury in ‘incipient AKI’. Nat Rev Nephrol. 2013;9(8):484–90.
Yun H, Sun Z, Wu J, Tang A, Hu M, Xiang Z. Laboratory data analysis of novel coronavirus (COVID-19) screening in 2510 patients. Clin Chim Acta. 2020;507:94–7.
Medeiros de Morais C d L, de Lima KM. A colorimetric microwell method using a desktop scanner for biochemical assays. Talanta. 2014;126:145–50.
Capitan-Vallvey LF, Lopez-Ruiz N, Martinez-Olmos A, Erenas MM, Palma AJ. Recent developments in computer vision-based analytical chemistry: a tutorial review. Anal Chim Acta. 2015;899:23–56.
Liu MM, Lian X, Liu H, Guo ZZ, Huang HH, Lei Y, et al. A colorimetric assay for sensitive detection of hydrogen peroxide and glucose in microfluidic paper-based analytical devices integrated with starch-iodide-gelatin system. Talanta. 2019;200:511–7.
Lee J, Lee YJ, Ahn YJ, Choi S, Lee G-J. A simple and facile paper-based colorimetric assay for detection of free hydrogen sulfide in prostate cancer cells. Sensor Actuator B - Chem. 2018;256:828–34.
Lin B, Yu Y, Cao Y, Guo M, Zhu D, Dai J, et al. Point-of-care testing for streptomycin based on aptamer recognizing and digital image colorimetry by smartphone. Biosens Bioelectron. 2018;100:482–9.
Zhang L, Wang H, Zhang X, Li X, Yu H-Z. Indirect competitive immunoassay on a Blu-ray disc for digitized quantitation of food toxins. ACS Sens. 2020;5(4):1239–45.
Liu J, Geng Z, Fan Z, Liu J, Chen H. Point-of-care testing based on smartphone: the current state-of-the-art (2017-2018). Biosens Bioelectron. 2019;132:17–37.
Wang J, Zhang L, Li X, Zhang X, Yu H-Z. From kirigami to three-dimensional paper-based micro-analytical device: cut-and-paste fabrication and mobile app quantitation. RSC Adv. 2019;9(40):23267–75.
Wang X, Li F, Cai Z, Liu K, Li J, Zhang B, et al. Sensitive colorimetric assay for uric acid and glucose detection based on multilayer-modified paper with smartphone as signal readout. Anal Bioanal Chem. 2018;410(10):2647–55.
Tian T, Bi Y, Xu X, Zhu Z, Yang C. Integrated paper-based microfluidic devices for point-of-care testing. Anal Methods. 2018;10(29):3567–81.
Jalal UM, Jin GJ, Shim JS. Paper-plastic hybrid microfluidic device for smartphone-based colorimetric analysis of urine. Anal Chem. 2017;89(24):13160–6.
Li X, Yang F, Wong JXH, Yu HZ. Integrated smartphone-app-chip system for on-site parts-per-billion-level colorimetric quantitation of aflatoxins. Anal Chem. 2017;89(17):8908–16.
Kong T, You JB, Zhang B, Nguyen B, Tarlan F, Jarvi K, et al. Accessory-free quantitative smartphone imaging of colorimetric paper-based assays. Lab Chip. 2019;19(11):1991–9.
Christodouleas DC, Nemiroski A, Kumar AA, Whitesides GM. Broadly available imaging devices enable high-quality low-cost photometry. Anal Chem. 2015;87(18):9170–8.
Soldat DJ, Barak P, Lepore BJ. Microscale colorimetric analysis using a desktop scanner and automated digital image analysis. J Chem Ed. 2009;86(5):617–20.
Kim DB, Hong JM, Chang S-K. Colorimetric determination of Cu2+ ions with a desktop scanner using silica nanoparticles via formation of a quinonediimine dye. Sensor Actuator B - Chem. 2017;252:537–43.
Meng X, Schultz CW, Cui C, Li X, Yu H-Z. On-site chip-based colorimetric quantitation of organophosphorus pesticides using an office scanner. Sensor Actuators B - Chem. 2015;215:577–83.
Wen J, Shi X, He Y, Zhou J, Li Y. Novel plastic biochips for colorimetric detection of biomolecules. Anal Bioanal Chem. 2012;404(6–7):1935–44.
Choi MG, Lee YJ, Chang IJ, Ryu H, Yoon S, Chang S-K. Flatbed-scanner-based colorimetric Cu2+ signaling system derived from a coumarin–benzopyrylium conjugated dye. Sensor Actuator B - Chem. 2018;268:22–8.
Gorocs Z, Ozcan A. Biomedical imaging and sensing using flatbed scanners. Lab Chip. 2014;14(17):3248–57.
Zhou H, Wang H, Li X, Leung VCM. A survey on mobile data offloading technologies. IEEE Access. 2018;6:5101–11.
Silva HA, Carraro JC, Bressan J, Hermsdorff HH. Relation between uric acid and metabolic syndrome in subjects with cardiometabolic risk. Einstein. 2015;13(2):202–8.
Krishnan E, Sokolove J. Uric acid in heart disease: a new C-reactive protein? Curr Opin Rheumatol. 2011;23(2):174–7.
De Backer G. European guidelines on cardiovascular disease prevention in clinical practice third joint task force of European and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of eight societies and by invited experts). Eur Heart J. 2003;24(17):1601–10.
Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, et al. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2011;123(20):2292–333.
Chan M, Bloomberg HM, Frieden T, Yusuf S, Davis S, Lackland D, et al. Hearts: technical package for cardiovascular disease management in primary health care. Switzerland: World Health Organization; 2016.
Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, et al. Heart disease and stroke statistics-2018 update: a report from the American Heart Association. Circulation. 2018;137(12):67–492.
Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, et al. Executive summary: heart disease and stroke statistics--2014 update: a report from the American Heart Association. Circulation. 2014;129(3):399–410.
Zhang L, Kwok H, Li X, Yu H-Z. Superhydrophobic substrates from off-the-shelf laboratory filter paper: simplified preparation, patterning, and assay application. ACS Appl Mater Interfaces. 2017;9(45):39728–35.
Pileggi JV, Giorgio J, Wybenga KD. A one-tube serum uric acid method using phosphotungstic acid as protein precipitant and color reagent. Clin Chim Acta. 1972;37:141–9.
Solnica B, Naskalski JW, Sieradzki J. The evaluation of analytical performance of the precision G point-of-care glucometer. Clin Chem Lab Med. 2001;39(12):1283–6.
Fossati P, Prencipe L. Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide. Clin Chem. 1982;28(10):2077–80.
Klotzsch SG, McNamara JR. Triglyceride measurements: a review of methods and interferences. Clin Chem. 1990;36(9):1605–13.
Long Q, Fang A, Wen Y, Li H, Zhang Y, Yao S. Rapid and highly-sensitive uric acid sensing based on enzymatic catalysis-induced upconversion inner filter effect. Biosens Bioelectron. 2016;86:109–14.
Wang J. Electrochemical glucose biosensors. Chem Rev. 2008;108:814–25.
Hasanah U, Sani NDM, Heng LY, Idroes R, Safitri E. Construction of a hydrogel pectin-based triglyceride optical biosensor with immobilized lipase enzymes. Biosensors. 2019;9(4):135–45.
We gratefully acknowledge the financial support from the Natural Science Foundation of China (Grant No. 21874098; 21575098); Shanxi Province International Cooperation Project (Grant No. 201903D421053); Shanxi Province University Scientific and Technological Achievements Transformation and Cultivation Project. This research was jointly supported by the Natural Sciences and Engineering Research Council (NSERC) of Canada.
All procedures performed in this work were in accordance with the protocols approved by the Biology and Medical Ethics Committee of Taiyuan University of Technology. The tested plasma samples were provided by the Shanxi Bethune Hospital with the consent from the patients and following the hospital’s regulation.
Conflict of interest
The authors have filed a China Patent (Application No. 201910668486.9) on July 23, 2019 to protect the IP disclosed in this publication.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Published in the topical collection Analytical Chemistry for Infectious Disease Detection and Prevention with guest editors Chaoyong Yang and XiuJun (James) Li.
About this article
Cite this article
Hou, P., Deng, R., Guo, J. et al. A WiFi scanner in conjunction with disposable multiplex paper assay for the quantitation of disease markers in blood plasma. Anal Bioanal Chem (2021). https://doi.org/10.1007/s00216-021-03234-6
- Point-of-care (POC) diagnosis
- Paper-based analytical device (PAD)
- Smartphone app