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Label-free electrochemical microfluidic biosensors: futuristic point-of-care analytical devices for monitoring diseases

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Abstract

The integration of microfluidics with electrochemical analysis has resulted in the development of single miniaturized detection systems, which allows the precise control of sample volume with multianalyte detection capability in a cost- and time-effective manner. Microfluidic electrochemical sensing devices (MESDs) can potentially serve as precise sensing and monitoring systems for the detection of molecular markers in various detrimental diseases. MESDs offer several advantages, including (i) automated sample preparation and detection, (ii) low sample and reagent requirement, (iii) detection of multianalyte in a single run, (iv) multiplex analysis in a single integrated device, and (v) portability with simplicity in application and disposability. Label-free MESDs can serve an affordable real-time detection with a simple analysis in a short processing time, providing point-of-care diagnosis/detection possibilities in precision medicine, and environmental analysis. In the current review, we elaborate on label-free microfluidic biosensors, provide comprehensive insights into electrochemical detection techniques, and discuss the principles of label-free microfluidic-based sensing approaches.

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References

  1. Whitesides GM (2006) The origins and the future of microfluidics. Nature 442:368–373. https://doi.org/10.1038/nature05058

    Article  CAS  PubMed  Google Scholar 

  2. Mou L, Jiang X (2017) Materials for microfluidic immunoassays: a review. Adv Healthc Mater 6:1601403. https://doi.org/10.1002/adhm.201601403

    Article  CAS  Google Scholar 

  3. Miao Q, Qi J, Li Y, Fan X, Deng D, Yan X et al (2021) Anchoring zinc-doped carbon dots on a paper-based chip for highly sensitive fluorescence detection of copper ions. Analyst 146:6297–6305. https://doi.org/10.1039/d1an01268a

    Article  CAS  PubMed  Google Scholar 

  4. Amirifar L, Besanjideh M, Nasiri R, Shamloo A, Nasrollahi F, de Barros NR et al (2022) Droplet-based microfluidics in biomedical applications. Biofabrication 14:022001. https://doi.org/10.1088/1758-5090/ac39a9

    Article  Google Scholar 

  5. Rettke D, Danneberg C, Neuendorf TA, Kuhn S, Friedrichs J, Hauck N et al (2022) Microfluidics-assisted synthesis and functionalization of monodisperse colloidal hydrogel particles for optomechanical biosensors. J Mater Chem B. https://doi.org/10.1039/d1tb02798k

    Article  PubMed  Google Scholar 

  6. Zhu C, Maldonado J, Sengupta K (2021) CMOS-based electrokinetic microfluidics with multi-modal cellular and bio-molecular sensing for end-to-end point-of-care system. IEEE Trans Biomed Circuits Syst 15:1250–1267. https://doi.org/10.1109/TBCAS.2021.3136165

    Article  PubMed  Google Scholar 

  7. Zhang S, Zahed MA, Sharifuzzaman M, Yoon S, Hui X, Chandra Barman S et al (2021) A wearable battery-free wireless and skin-interfaced microfluidics integrated electrochemical sensing patch for on-site biomarkers monitoring in human perspiration. Biosens Bioelectron 175:112844. https://doi.org/10.1016/j.bios.2020.112844

    Article  CAS  PubMed  Google Scholar 

  8. Vasudev A, Kaushik A, Tomizawa Y, Norena N, Bhansali S (2013) An LTCC-based microfluidic system for label-free, electrochemical detection of cortisol. Sens Actuators B Chem 182:139–146. https://doi.org/10.1016/j.snb.2013.02.096

    Article  CAS  Google Scholar 

  9. Ben-Yoav H, Dykstra PH, Bentley WE, Ghodssi R (2012) A microfluidic-based electrochemical biochip for label-free diffusion-restricted DNA hybridization analysis. Biosens Bioelectron 38:114–120. https://doi.org/10.1016/j.bios.2012.05.009

    Article  CAS  PubMed  Google Scholar 

  10. Labib M, Sargent EH, Kelley SO (2016) Electrochemical methods for the analysis of clinically relevant biomolecules. Chem Rev 116:9001–9090. https://doi.org/10.1021/acs.chemrev.6b00220

    Article  CAS  PubMed  Google Scholar 

  11. Felix FS, Angnes L (2018) Electrochemical immunosensors–a powerful tool for analytical applications. Biosens Bioelectron 102:470–478. https://doi.org/10.1016/j.bios.2017.11.029

    Article  CAS  PubMed  Google Scholar 

  12. Shin SR, Kilic T, Zhang YS, Avci H, Hu N, Kim D et al (2017) Label-free and regenerative electrochemical microfluidic biosensors for continual monitoring of cell Secretomes. Adv Sci 4:1600522. https://doi.org/10.1002/advs.201600522

    Article  CAS  Google Scholar 

  13. Yu X, Xu D, Cheng Q (2006) Label-free detection methods for protein microarrays. Proteomics 6:5493–5503. https://doi.org/10.1002/pmic.200600216

    Article  CAS  PubMed  Google Scholar 

  14. Rhouati A, Catanante G, Nunes G, Hayat A, Marty J-L (2016) Label-free aptasensors for the detection of mycotoxins. Sensors 16:2178. https://doi.org/10.3390/s16122178

    Article  CAS  PubMed Central  Google Scholar 

  15. Nge PN, Rogers CI, Woolley AT (2013) Advances in microfluidic materials, functions, integration, and applications. Chem Rev 113:2550–2583. https://doi.org/10.1021/cr300337x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Lin C-H, Lee G-B, Lin Y-H, Chang G-L (2001) A fast prototyping process for fabrication of microfluidic systems on soda-lime glass. J Micromech Microeng 11:726. https://doi.org/10.1088/0960-1317/11/6/316

    Article  CAS  Google Scholar 

  17. Washburn AL, Gunn LC, Bailey RC (2009) Label-free quantitation of a cancer biomarker in complex media using silicon photonic microring resonators. Anal Chem 81:9499–9506. https://doi.org/10.1021/ac902006p

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ren K, Zhou J, Wu H (2013) Materials for microfluidic chip fabrication. Acc Chem Res 46:2396–2406. https://doi.org/10.1021/ar300314s

    Article  CAS  PubMed  Google Scholar 

  19. Quinn DJ, Spearing SM, Ashby MF, Fleck NA (2006) A systematic approach to process selection in MEMS. J Microelectromech Syst 15:1039–1050. https://doi.org/10.1109/JMEMS.2006.880292

    Article  Google Scholar 

  20. Iliescu C, Taylor H, Avram M, Miao J, Franssila S (2012) A practical guide for the fabrication of microfluidic devices using glass and silicon. Biomicrofluidics 6:016505. https://doi.org/10.1063/1.3689939

    Article  CAS  PubMed Central  Google Scholar 

  21. Nawrot W, Malecha K (2020) Biomaterial embedding process for ceramic–polymer microfluidic sensors. Sensors 20:1745. https://doi.org/10.3390/s20061745

    Article  CAS  PubMed Central  Google Scholar 

  22. Pandey CM, Augustine S, Kumar S, Kumar S, Nara S, Srivastava S et al (2018) Microfluidics based point-of-care diagnostics. Biotechnol J 13:1700047. https://doi.org/10.1002/biot.201700047

    Article  CAS  Google Scholar 

  23. Herzberger J, Sirrine JM, Williams CB, Long TE (2019) Polymer design for 3D printing elastomers: recent advances in structure, properties, and printing. Prog Polym Sci 97:101144. https://doi.org/10.1016/j.progpolymsci.2019.101144

    Article  CAS  Google Scholar 

  24. Becker H, Gärtner C (2008) Polymer microfabrication technologies for microfluidic systems. Anal Bioanal Chem 390:89–111. https://doi.org/10.1007/s00216-007-1692-2

    Article  CAS  PubMed  Google Scholar 

  25. Martinez AW, Phillips ST, Butte MJ, Whitesides GM (2007) Patterned paper as a platform for inexpensive, low-volume, portable bioassays. Angew Chem Int Ed Engl 46:1318–1320. https://doi.org/10.1002/anie.200603817

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Jiang X, Fan ZH (2016) Fabrication and operation of paper-based analytical devices. Annu Rev Anal Chem 9:203–222. https://doi.org/10.1146/annurev-anchem-071015-041714

    Article  Google Scholar 

  27. Ebrahimi M, Johari-Ahar M, Hamzeiy H, Barar J, Mashinchian O, Omidi Y (2012) Electrochemical impedance spectroscopic sensing of methamphetamine by a specific aptamer. Bioimpacts 2:91–95. https://doi.org/10.5681/bi.2012.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Saberian-Borujeni M, Johari-Ahar M, Hamzeiy H, Barar J, Omidi Y (2014) Nanoscaled aptasensors for multi-analyte sensing. Bioimpacts 4:205–215. https://doi.org/10.15171/bi.2014.015

  29. Johari-Ahar M, Rashidi MR, Barar J, Aghaie M, Mohammadnejad D, Ramazani A et al (2015) An ultra-sensitive impedimetric immunosensor for detection of the serum oncomarker CA-125 in ovarian cancer patients. Nanoscale 7:3768–3779. https://doi.org/10.1039/c4nr06687a

    Article  CAS  PubMed  Google Scholar 

  30. Fathi F, Ezzati Nazhad Dolatanbadi J, Rashidi MR, Omidi Y (2016) Kinetic studies of bovine serum albumin interaction with PG and TBHQ using surface plasmon resonance. Int J Biol Macromol 91:1045–1050. https://doi.org/10.1016/j.ijbiomac.2016.06.054

    Article  CAS  PubMed  Google Scholar 

  31. Majidi MR, Omidi Y, Karami P, Johari-Ahar M (2016) Reusable potentiometric screen-printed sensor and label-free aptasensor with pseudo-reference electrode for determination of tryptophan in the presence of tyrosine. Talanta 150:425–433. https://doi.org/10.1016/j.talanta.2015.12.064

    Article  CAS  PubMed  Google Scholar 

  32. Karami P, Majidi MR, Johari-Ahar M, Barar J, Omidi Y (2017) Development of screen-printed tryptophan-kynurenine immunosensor for in vitro assay of kynurenine-mediated immunosuppression effect of cancer cells on activated T-cells. Biosens Bioelectron 92:287–293. https://doi.org/10.1016/j.bios.2016.11.010

    Article  CAS  PubMed  Google Scholar 

  33. Pakchin PS, Nakhjavani SA, Saber R, Ghanbari H, Omidi Y (2017) Recent advances in simultaneous electrochemical multi-analyte sensing platforms. Trends Anal Chem 92:32–41. https://doi.org/10.1016/j.trac.2017.04.010

    Article  CAS  Google Scholar 

  34. Akbari Nakhjavani S, Khalilzadeh B, Samadi Pakchin P, Saber R, Ghahremani MH, Omidi Y (2018) A highly sensitive and reliable detection of CA15-3 in patient plasma with electrochemical biosensor labeled with magnetic beads. Biosens Bioelectron 122:8–15. https://doi.org/10.1016/j.bios.2018.08.047

    Article  CAS  PubMed  Google Scholar 

  35. Samadi Pakchin P, Ghanbari H, Saber R, Omidi Y (2018) Electrochemical immunosensor based on chitosan-gold nanoparticle/carbon nanotube as a platform and lactate oxidase as a label for detection of CA125 oncomarker. Biosens Bioelectron 122:68–74. https://doi.org/10.1016/j.bios.2018.09.016

    Article  CAS  PubMed  Google Scholar 

  36. Akbari Nakhjavani S, Afsharan H, Khalilzadeh B, Ghahremani MH, Carrara S, Omidi Y (2019) Gold and silver bio/nano-hybrids-based electrochemical immunosensor for ultrasensitive detection of carcinoembryonic antigen. Biosens Bioelectron 141:111439. https://doi.org/10.1016/j.bios.2019.111439

    Article  CAS  PubMed  Google Scholar 

  37. Fathi F, Rashidi MR, Omidi Y (2019) Ultra-sensitive detection by metal nanoparticles-mediated enhanced SPR biosensors. Talanta 192:118–127. https://doi.org/10.1016/j.talanta.2018.09.023

    Article  CAS  PubMed  Google Scholar 

  38. Hashemzadeh S, Omidi Y, Rafii-Tabar H (2019) Amperometric lactate nanobiosensor based on reduced graphene oxide, carbon nanotube and gold nanoparticle nanocomposite. Mikrochim Acta 186:680. https://doi.org/10.1007/s00604-019-3791-0

    Article  CAS  PubMed  Google Scholar 

  39. Jalilzadeh-Razin S, Mantegi M, Tohidkia MR, Pazhang Y, Pourseif MM, Barar J et al (2019) Phage antibody library screening for the selection of novel high-affinity human single-chain variable fragment against gastrin receptor: an in silico and in vitro study. Daru 27:21–34. https://doi.org/10.1007/s40199-018-0233-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Samadi Pakchin P, Fathi M, Ghanbari H, Saber R, Omidi Y (2020) A novel electrochemical immunosensor for ultrasensitive detection of CA125 in ovarian cancer. Biosens Bioelectron 153:112029. https://doi.org/10.1016/j.bios.2020.112029

    Article  CAS  PubMed  Google Scholar 

  41. Rivas L, Mayorga-Martinez CC, Quesada-González D, Zamora-Gálvez A, de la Escosura-Muñiz A, Merkoçi A (2015) Label-free impedimetric aptasensor for ochratoxin–a detection using iridium oxide nanoparticles. Anal Chem 87:5167–5172. https://doi.org/10.1021/acs.analchem.5b00890

    Article  CAS  PubMed  Google Scholar 

  42. Hua X, Xia H-L, Long Y-T (2019) Revisiting a classical redox process on a gold electrode by operando ToF-SIMS: where does the gold go? Chem Sci 10:6215–6219. https://doi.org/10.1039/C9SC00956F

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ji X, Chan PK (2017) Highly sensitive glucose sensor based on organic electrochemical transistor with modified gate electrode. Springer, Biosensors and Biodetection, pp 205–216

    Google Scholar 

  44. Pappa AM, Curto VF, Braendlein M, Strakosas X, Donahue MJ, Fiocchi M et al (2016) Organic transistor arrays integrated with finger-powered microfluidics for multianalyte saliva testing. Adv Healthc Mater 5:2295–2302. https://doi.org/10.1002/adhm.201600494

    Article  CAS  PubMed  Google Scholar 

  45. Lin P, Luo X, Hsing IM, Yan F (2011) Organic electrochemical transistors integrated in flexible microfluidic systems and used for label-free DNA sensing. Adv Mater 23:4035–4040. https://doi.org/10.1002/adma.201102017

    Article  CAS  PubMed  Google Scholar 

  46. Zhang G-J, Chua JH, Chee R-E, Agarwal A, Wong SM (2009) Label-free direct detection of MiRNAs with silicon nanowire biosensors. Biosens Bioelectron 24:2504–2508. https://doi.org/10.1016/j.bios.2008.12.035

    Article  CAS  PubMed  Google Scholar 

  47. Yeor-Davidi E, Zverzhinetsky M, Krivitsky V, Patolsky F (2020) Real-time monitoring of bacterial biofilms metabolic activity by a redox-reactive nanosensors array. J Nanobiotechnol 18:1–11. https://doi.org/10.1186/s12951-020-00637-y

    Article  CAS  Google Scholar 

  48. Shiau AK, Massari ME, Ozbal CC (2008) Back to basics: label-free technologies for small molecule screening. Comb Chem High Throughput Screening 11:231–237. https://doi.org/10.2174/138620708783877807

    Article  CAS  Google Scholar 

  49. Grieshaber D, MacKenzie R, Vörös J, Reimhult E (2008) Electrochemical biosensors-sensor principles and architectures Sensors 8:1400–1458. https://doi.org/10.3390/s80314000

    Article  CAS  PubMed  Google Scholar 

  50. Kellens E, Bové H, Vandenryt T, Lambrichts J, Dekens J, Drijkoningen S et al (2018) Micro-patterned molecularly imprinted polymer structures on functionalized diamond-coated substrates for testosterone detection. Biosens Bioelectron 118:58–65. https://doi.org/10.1016/j.bios.2018.07.032

    Article  CAS  PubMed  Google Scholar 

  51. Ogata AF, Edgar JM, Majumdar S, Briggs JS, Patterson SV, Tan MX et al (2017) Virus-enabled biosensor for human serum albumin. Anal Chem 89:1373–1381. https://doi.org/10.1021/acs.analchem.6b04840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Narang J, Malhotra N, Singhal C, Mathur A, Pundir C (2017) Detection of alprazolam with a lab on paper economical device integrated with urchin like Ag@ Pd shell nano-hybrids. Mater Sci Eng C 80:728–735. https://doi.org/10.1016/j.msec.2016.11.128

    Article  CAS  Google Scholar 

  53. Ben-Yoav H, Dykstra PH, Bentley WE, Ghodssi R (2015) A controlled microfluidic electrochemical lab-on-a-chip for label-free diffusion-restricted DNA hybridization analysis. Biosens Bioelectron 64:579–585. https://doi.org/10.1016/j.bios.2014.09.069

    Article  CAS  PubMed  Google Scholar 

  54. Nwankire CE, Venkatanarayanan A, Glennon T, Keyes TE, Forster RJ, Ducree J (2015) Label-free impedance detection of cancer cells from whole blood on an integrated centrifugal microfluidic platform. Biosens Bioelectron 68:382–389. https://doi.org/10.1016/j.bios.2014.12.049

    Article  CAS  PubMed  Google Scholar 

  55. Channon RB, Yang Y, Feibelman KM, Geiss BJ, Dandy DS, Henry CS (2018) Development of an electrochemical paper-based analytical device for trace detection of virus particles. Anal Chem 90:7777–7783. https://doi.org/10.1021/acs.analchem.8b02042

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Qi J, Li B, Zhou N, Wang X, Deng D, Luo L et al (2019) The strategy of antibody-free biomarker analysis by in-situ synthesized molecularly imprinted polymers on movable valve paper-based device. Biosens Bioelectron 142:111533. https://doi.org/10.1016/j.bios.2019.111533

    Article  CAS  PubMed  Google Scholar 

  57. Siavash Moakhar R, AbdelFatah T, Sanati A, Jalali M, Flynn SE, Mahshid SS et al (2020) A nanostructured gold/graphene microfluidic device for direct and plasmonic-assisted impedimetric detection of bacteria. ACS Appl Mater Interfaces 12:23298–23310. https://doi.org/10.1021/acsami.0c02654

    Article  CAS  PubMed  Google Scholar 

  58. Zhao H, Liu M, Jiang T, Xu J, Zhang H, Yu C et al (2020) Ultrasensitive monitoring of DNA damage associated with free radicals exposure using dynamic carbon nanotubes bridged interdigitated electrode array. Environ Int 139:105672. https://doi.org/10.1016/j.envint.2020.105672

    Article  CAS  PubMed  Google Scholar 

  59. Sanghavi BJ, Moore JA, Chávez JL, Hagen JA, Kelley-Loughnane N, Chou C-F et al (2016) Aptamer-functionalized nanoparticles for surface immobilization-free electrochemical detection of cortisol in a microfluidic device. Biosens Bioelectron 78:244–252. https://doi.org/10.1016/j.bios.2015.11.044

    Article  CAS  PubMed  Google Scholar 

  60. Wang Y, Xu H, Luo J, Liu J, Wang L, Fan Y et al (2016) A novel label-free microfluidic paper-based immunosensor for highly sensitive electrochemical detection of carcinoembryonic antigen. Biosens Bioelectron 83:319–326. https://doi.org/10.1016/j.bios.2016.04.062

    Article  CAS  PubMed  Google Scholar 

  61. Yukird J, Soum V, Kwon O-S, Shin K, Chailapakul O, Rodthongkum N (2020) 3D paper-based microfluidic device: a novel dual-detection platform of bisphenol A. Analyst 145:1491–1498. https://doi.org/10.1039/C9AN01738K

    Article  CAS  PubMed  Google Scholar 

  62. Hossain MM, Moon J-M, Gurudatt N, Park D-S, Choi CS, Shim Y-B (2019) Separation detection of hemoglobin and glycated hemoglobin fractions in blood using the electrochemical microfluidic channel with a conductive polymer composite sensor. Biosens Bioelectron 142:111515. https://doi.org/10.1016/j.bios.2019.111515

    Article  CAS  Google Scholar 

  63. Sempionatto JR, Brazaca LC, García-Carmona L, Bolat G, Campbell AS, Martin A et al (2019) Eyeglasses-based tear biosensing system: non-invasive detection of alcohol, vitamins and glucose. Biosens Bioelectron 137:161–170. https://doi.org/10.1016/j.bios.2019.04.058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Boobphahom S, Ruecha N, Rodthongkum N, Chailapakul O, Remcho VT (2019) A copper oxide-ionic liquid/reduced graphene oxide composite sensor enabled by digital dispensing: non-enzymatic paper-based microfluidic determination of creatinine in human blood serum. Anal Chim Acta 1083:110–118. https://doi.org/10.1016/j.aca.2019.07.029

    Article  CAS  PubMed  Google Scholar 

  65. Bae CW, Toi PT, Kim BY, Lee WI, Lee HB, Hanif A et al (2019) Fully stretchable capillary microfluidics-integrated nanoporous gold electrochemical sensor for wearable continuous glucose monitoring. ACS Appl Mater Interfaces 11:14567–14575. https://doi.org/10.1021/acsami.9b00848

    Article  CAS  PubMed  Google Scholar 

  66. Singh R, Hong S, Jang J (2017) Label-free detection of influenza viruses using a reduced graphene oxide-based electrochemical immunosensor integrated with a microfluidic platform. Sci Rep 7:42771. https://doi.org/10.1038/srep42771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Chiu DT, deMello AJ, Di Carlo D, Doyle PS, Hansen C, Maceiczyk RM et al (2017) Small but perfectly formed? Successes, challenges, and opportunities for microfluidics in the chemical and biological sciences. Chem 2:201–223. https://doi.org/10.1016/j.chempr.2017.01.009

    Article  CAS  Google Scholar 

  68. Narang J, Malhotra N, Singhal C, Mathur A, Pn AK, Pundir C (2017) Detection of alprazolam with a lab on paper economical device integrated with urchin like Ag@ Pd shell nano-hybrids. Mater Sci Eng C 80:728–735. https://doi.org/10.1016/j.msec.2016.11.128

    Article  CAS  Google Scholar 

  69. Hong SA, Kim Y-J, Kim SJ, Yang S (2018) Electrochemical detection of methylated DNA on a microfluidic chip with nanoelectrokinetic pre-concentration. Biosens Bioelectron 107:103–110. https://doi.org/10.1016/j.bios.2018.01.067

    Article  CAS  PubMed  Google Scholar 

  70. Parra-Cabrera C, Samitier J, Homs-Corbera A (2016) Multiple biomarkers biosensor with just-in-time functionalization: application to prostate cancer detection. Biosens Bioelectron 77:1192–1200. https://doi.org/10.1016/j.bios.2015.10.064

    Article  CAS  PubMed  Google Scholar 

  71. Chiriacò MS, Luvisi A, Primiceri E, Sabella E, De Bellis L, Maruccio G (2018) Development of a lab-on-a-chip method for rapid assay of Xylella fastidiosa subsp. pauca strain CoDiRO. Sci Rep 8:1–8. https://doi.org/10.1038/s41598-018-25747-4

    Article  CAS  Google Scholar 

  72. Wang R, Xu Y, Sors T, Irudayaraj J, Ren W, Wang R (2018) Impedimetric detection of bacteria by using a microfluidic chip and silver nanoparticle based signal enhancement. Microchim Acta 185:184. https://doi.org/10.1007/s00604-017-2645-x

    Article  CAS  Google Scholar 

  73. Siller IG, Preuss J-A, Urmann K, Hoffmann MR, Scheper T, Bahnemann J (2020) 3D-printed flow cells for aptamer-based impedimetric detection of E. coli crooks strain. Sensors 20:4421. https://doi.org/10.3390/s20164421

  74. Ma W, Liu L, Xu Y, Wang L, Chen L, Yan S et al (2020) A highly efficient preconcentration route for rapid and sensitive detection of endotoxin based on an electrochemical biosensor. Analyst 145:4204–4211. https://doi.org/10.1039/D0AN00315H

    Article  CAS  PubMed  Google Scholar 

  75. Dos Santos MB, Queirós RB, Geraldes Á, Marques C, Vilas-Boas V, Dieguez L et al (2019) Portable sensing system based on electrochemical impedance spectroscopy for the simultaneous quantification of free and total microcystin-LR in freshwaters. Biosens Bioelectron 142:111550. https://doi.org/10.1016/j.bios.2019.111550

    Article  CAS  Google Scholar 

  76. Núnez-Bajo E, Blanco-López MC, Costa-García A, Fernández-Abedul MT (2017) Integration of gold-sputtered electrofluidic paper on wire-included analytical platforms for glucose biosensing. Biosens Bioelectron 91:824–832. https://doi.org/10.1016/j.bios.2017.01.029

    Article  CAS  PubMed  Google Scholar 

  77. Narang J, Singhal C, Mathur A, Khanuja M, Varshney A, Garg K et al (2017) Lab on paper chip integrated with Si@ GNRs for electroanalysis of diazepam. Anal Chim Acta 980:50–57. https://doi.org/10.1016/j.aca.2017.05.006

    Article  CAS  PubMed  Google Scholar 

  78. Liu J, Zhang Y, Jiang M, Tian L, Sun S, Zhao N et al (2017) Electrochemical microfluidic chip based on molecular imprinting technique applied for therapeutic drug monitoring. Biosens Bioelectron 91:714–720. https://doi.org/10.1016/j.bios.2017.01.037

    Article  CAS  PubMed  Google Scholar 

  79. Park YM, Lim SY, Shin SJ, Kim CH, Jeong SW, Shin SY et al (2018) A film-based integrated chip for gene amplification and electrochemical detection of pathogens causing foodborne illnesses. Anal Chim Acta 1027:57–66. https://doi.org/10.1016/j.aca.2018.03.061

    Article  CAS  PubMed  Google Scholar 

  80. Safavieh M, Ahmed MU, Tolba M, Zourob M (2012) Microfluidic electrochemical assay for rapid detection and quantification of Escherichia coli. Biosens Bioelectron 31:523–528. https://doi.org/10.1016/j.bios.2011.11.032

    Article  CAS  PubMed  Google Scholar 

  81. Thiha A, Ibrahim F, Muniandy S, Dinshaw IJ, Teh SJ, Thong KL et al (2018) All-carbon suspended nanowire sensors as a rapid highly-sensitive label-free chemiresistive biosensing platform. Biosens Bioelectron 107:145–152. https://doi.org/10.1016/j.bios.2018.02.024

    Article  CAS  PubMed  Google Scholar 

  82. Laribi A, Allegra S, Souiri M, Mzoughi R, Othmane A, Girardot F (2020) Legionella pneumophila sg1-sensing signal enhancement using a novel electrochemical immunosensor in dynamic detection mode. Talanta 215:120904. https://doi.org/10.1016/j.talanta.2020.120904

    Article  CAS  PubMed  Google Scholar 

  83. Wang Y, Luo J, Liu J, Sun S, Xiong Y, Ma Y et al (2019) Label-free microfluidic paper-based electrochemical aptasensor for ultrasensitive and simultaneous multiplexed detection of cancer biomarkers. Biosens Bioelectron 136:84–90. https://doi.org/10.1016/j.bios.2019.04.032

    Article  CAS  PubMed  Google Scholar 

  84. Fan Y, Liu J, Wang Y, Luo J, Xu H, Xu S et al (2017) A wireless point-of-care testing system for the detection of neuron-specific enolase with microfluidic paper-based analytical devices. Biosens Bioelectron 95:60–66. https://doi.org/10.1016/j.bios.2017.04.003

    Article  CAS  PubMed  Google Scholar 

  85. Wei B, Mao K, Liu N, Zhang M, Yang Z (2018) Graphene nanocomposites modified electrochemical aptamer sensor for rapid and highly sensitive detection of prostate specific antigen. Biosens Bioelectron 121:41–46. https://doi.org/10.1016/j.bios.2018.08.067

    Article  CAS  PubMed  Google Scholar 

  86. Ming T, Wang Y, Luo J, Liu J, Sun S, Xing Y et al (2019) Folding paper-based aptasensor platform coated with novel nanoassemblies for instant and highly sensitive detection of 17β-estradiol. ACS Sens 4:3186–3194. https://doi.org/10.1021/acssensors.9b01633

    Article  CAS  PubMed  Google Scholar 

  87. Xie Y, Zhi X, Su H, Wang K, Yan Z, He N et al (2015) A novel electrochemical microfluidic chip combined with multiple biomarkers for early diagnosis of gastric cancer. Nanoscale Res Lett 10:477. https://doi.org/10.1186/s11671-015-1153-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Garg M, Christensen MG, Iles A, Sharma AL, Singh S, Pamme N (2020) Microfluidic-based electrochemical immunosensing of ferritin. Biosensors 10:91. https://doi.org/10.3390/bios10080091

    Article  CAS  PubMed Central  Google Scholar 

  89. Moon J-M, Kim D-M, Kim MH, Han J-Y, Jung D-K, Shim Y-B (2017) A disposable amperometric dual-sensor for the detection of hemoglobin and glycated hemoglobin in a finger prick blood sample. Biosens Bioelectron 91:128–135. https://doi.org/10.1016/j.bios.2016.12.038

    Article  CAS  PubMed  Google Scholar 

  90. Ramalingam S, Chand R, Singh CB, Singh A (2019) Phosphorene-gold nanocomposite based microfluidic aptasensor for the detection of okadaic acid. Biosens Bioelectron 135:14–21. https://doi.org/10.1016/j.bios.2019.03.056

    Article  CAS  PubMed  Google Scholar 

  91. Lu L, Gunasekaran S (2019) Dual-channel ITO-microfluidic electrochemical immunosensor for simultaneous detection of two mycotoxins. Talanta 194:709–716. https://doi.org/10.1016/j.talanta.2018.10.091

    Article  CAS  PubMed  Google Scholar 

  92. Singh N, Ali MA, Rai P, Ghori I, Sharma A, Malhotra B et al (2020) Dual-modality microfluidic biosensor based on nanoengineered mesoporous graphene hydrogels. Lab Chip 20:760–777. https://doi.org/10.1039/C9LC00751B

    Article  CAS  PubMed  Google Scholar 

  93. Cincotto FH, Fava EL, Moraes FC, Fatibello-Filho O, Faria RC (2019) A new disposable microfluidic electrochemical paper-based device for the simultaneous determination of clinical biomarkers. Talanta 195:62–68. https://doi.org/10.1016/j.talanta.2018.11.022

    Article  CAS  PubMed  Google Scholar 

  94. Zhu L, Liu X, Yang J, He Y, Li Y (2020) Application of multiplex microfluidic electrochemical sensors in monitoring hematological tumor biomarkers. Anal Chem 92:11981–11986. https://doi.org/10.1021/acs.analchem.0c02430

    Article  CAS  PubMed  Google Scholar 

  95. Triroj N, Saensak R, Porntheeraphat S, Paosawatyanyong B, Amornkitbamrung V (2020) Diamond-like carbon thin film electrodes for microfluidic bioelectrochemical sensing platforms. Anal Chem 92:3650–3657. https://doi.org/10.1021/acs.analchem.9b04689

    Article  CAS  PubMed  Google Scholar 

  96. Fava EL, Silva TA, do Prado TM, de Moraes FC, Faria RC, Fatibello-Filho O. (2019) Electrochemical paper-based microfluidic device for high throughput multiplexed analysis. Talanta 203:280–286. https://doi.org/10.1016/j.talanta.2019.05.081

    Article  CAS  PubMed  Google Scholar 

  97. Alizadeh N, Salimi A, Sham T-K, Bazylewski P, Fanchini G (2020) Intrinsic enzyme-like activities of cerium oxide nanocomposite and its application for extracellular H2O2 detection using an electrochemical microfluidic device. ACS Omega 5:11883–11894. https://doi.org/10.1021/acsomega.9b03252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Martín A, Kim J, Kurniawan JF, Sempionatto JR, Moreto JR, Tang G et al (2017) Epidermal microfluidic electrochemical detection system: enhanced sweat sampling and metabolite detection. ACS Sens 2:1860–1868. https://doi.org/10.1021/acssensors.7b00729

    Article  CAS  PubMed  Google Scholar 

  99. Lee M-H, O’Hare D, Chen Y-L, Chang Y-C, Yang C-H, Liu B-D et al (2014) Molecularly imprinted electrochemical sensing of urinary melatonin in a microfluidic system. Biomicrofluidics 8:054115. https://doi.org/10.1063/1.4898152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Aymerich J, Márquez A, Terés L, Muñoz-Berbel X, Jiménez C, Domínguez C et al (2018) Cost-effective smartphone-based reconfigurable electrochemical instrument for alcohol determination in whole blood samples. Biosens Bioelectron 117:736–742. https://doi.org/10.1016/j.bios.2018.06.044

    Article  CAS  PubMed  Google Scholar 

  101. Lamas-Ardisana P, Martínez-Paredes G, Añorga L, Grande H (2018) Glucose biosensor based on disposable electrochemical paper-based transducers fully fabricated by screen-printing. Biosens Bioelectron 109:8–12. https://doi.org/10.1016/j.bios.2018.02.061

    Article  CAS  PubMed  Google Scholar 

  102. Gu S, Lu Y, Ding Y, Li L, Song H, Wang J et al (2014) A droplet-based microfluidic electrochemical sensor using platinum-black microelectrode and its application in high sensitive glucose sensing. Biosens Bioelectron 55:106–112. https://doi.org/10.1016/j.bios.2013.12.002

    Article  CAS  PubMed  Google Scholar 

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Funding

The authors like to acknowledge the Research Center for Pharmaceutical Nanotechnology at Tabriz University of Medical Sciences for supporting this PhD thesis (# 63766).

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Authors and Affiliations

  1. Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran

    Ghasem Ebrahimi & Parvin Samadi Pakchin

  2. Department of Biochemistry and Clinical Laboratories, Faculty of Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Ghasem Ebrahimi & Ali Mota

  3. School of Mechanical Engineering, Sharif University of Technology, Tehran, Iran

    Amir Shamloo

  4. Department of Analytical Chemistry, University of Valencia, Valencia, Spain

    Miguel de la Guardia

  5. Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, 33328, USA

    Hossein Omidian & Yadollah Omidi

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  1. Ghasem Ebrahimi
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  2. Parvin Samadi Pakchin
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  3. Amir Shamloo
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  4. Ali Mota
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  5. Miguel de la Guardia
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Correspondence to Yadollah Omidi.

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Ebrahimi, G., Samadi Pakchin, P., Shamloo, A. et al. Label-free electrochemical microfluidic biosensors: futuristic point-of-care analytical devices for monitoring diseases. Microchim Acta 189, 252 (2022). https://doi.org/10.1007/s00604-022-05316-3

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  • DOI: https://doi.org/10.1007/s00604-022-05316-3

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