Microfluidics and Nanofluidics

, Volume 16, Issue 5, pp 887–894 | Cite as

Thread-based microfluidic system for detection of rapid blood urea nitrogen in whole blood

  • Yu-An Yang
  • Che-Hsin LinEmail author
  • Yi-Chi Wei
Research Paper


This study develops a thread-based microfluidic device with variable volume injection capability and 3-dimensional (3D) detection electrodes for capillary electrophoresis electrochemical (CE–EC) detection of blood urea nitrogen (BUN) in whole blood. A poly methyl methacrylate (PMMA) substrate with concave 3D electrodes produced by the hot embossing method is used to enhance the sensing performance of the CE–EC system. Results show that the chip with 3D sensing electrodes exhibits a measured current response nine times higher and signal-to-noise ratio five times higher when compared to the peak responses obtained using a chip with conventional 2D sensing electrodes. In addition, the developed thread-based microfluidic system is capable of injecting variable sample volumes into the separation thread simply by wrapping the injection thread different numbers of times around the separation thread. The peak S/N ratio can be further enhanced with this simple approach. Results also indicate that the CE–EC system exhibits good linear dynamic range for detecting a urea sample in concentrations from 0.1 to 10.0 mM (R 2 = 0.9848), which is suitable for adoption in detecting the BUN concentration in human blood (1.78–7.12 mM). Separation and detection of the ammonia ions converted from BUN in whole blood is successfully demonstrated in the present study, with the developed thread-based microfluidic system providing a low-cost, high-performance method for detecting BUN in human blood.


Blood urea nitrogen Thread-based microfluidic system Variable volume injection Capillary electrophoresis Whole blood 


  1. Ballerini DR, Li X, Shen W (2011) Flow control concepts for thread-based microfluidic devices. Biomicrofluidics 5:14105CrossRefGoogle Scholar
  2. Becker H, Gartner C (2001) Polymer based micro-reactors. J Biotechnol 82:89–99Google Scholar
  3. Becker H, Dietz W, Dannberg P (1998) Microfluidic manifolds by polymer hot embossing for μ-TAS applications. In: Proceedings of the 2nd international conference on miniaturized systems for chemistry and life sciences (µTAS 98), pp 253–256Google Scholar
  4. Bhandari P, Narahari T, Dendukuri D (2011) ‘Fab-Chips’: a versatile, fabric-based platform for low-cost, rapid and multiplexed diagnostics. Lab Chip 11:2493–2499CrossRefGoogle Scholar
  5. Cauthen CA, Lipinski MJ, Abbate A, Appleton D, Nusca A, Varma A, Goudreau E, Cowley MJ, Vetrovec GW (2008) Relation of blood urea nitrogen to long-term mortality in patients with heart failure. Am J Cardiol 101:1643–1647CrossRefGoogle Scholar
  6. Chen CM, Chang GL, Lin CH (2008) Performance evaluation of a capillary electrophoresis electrochemical chip integrated with gold nanoelectrode ensemble working and decoupler electrodes. J Chromatogr A 1194:231–236CrossRefGoogle Scholar
  7. Chiang TY, Lin CH (2014) A microfluidic chip for ammonium sensing incorporating ion-selective membranes formed by surface tension forces. RSC Advances 4:379–385Google Scholar
  8. Dahlin AP, Wetterhall M, Liljegren G, Bergstrom SK, Andren P, Nyholm L, Markides KE, Bergquist J (2005) Capillary electrophoresis coupled to mass spectrometry from a polymer modified poly(dimethylsiloxane) microchip with an integrated graphite electrospray tip. Analyst 130:193–199CrossRefGoogle Scholar
  9. Delinger SL, Davis JM (1992) Influence of analyte plug width on plate number in capillary electrophoresis. Anal Chem 64:1947–1959CrossRefGoogle Scholar
  10. Dungchai W, Chailapakul O, Henry CS (2011) A low-cost, simple, and rapid fabrication method for paper-based microfluidics using wax screen-printing. Analyst 136:77–82CrossRefGoogle Scholar
  11. Effenhauser CS, Manz A, Widmer HM (1993) Glass chips for high-speed capillary electrophoresis separations with submicrometer plate heights. Anal Chem 65:2637–2642CrossRefGoogle Scholar
  12. Harrison DJ, Manz A, Fan ZH, Ludi H, Widmer HM (1992) Capillary electrophoresis and sample injection systems integrated on a planar glass chip. Anal Chem 64:1926–1932CrossRefGoogle Scholar
  13. Honda N, Inaba M, Katagiri T, Shoji S, Sato H, Homma T, Osaka T, Saito M, Mizuno J, Wada Y (2005) High efficiency electrochemical immuno sensors using 3D comb electrodes. Biosens Bioelectron 20:2306–2309CrossRefGoogle Scholar
  14. Horng RH, Han P, Chen HY, Lin KW, Tsai TM, Zen JM (2005) PMMA-based capillary electrophoresis electrochemical detection microchip fabrication. J Micromech Microeng 15:6–10CrossRefGoogle Scholar
  15. Hsieh B-C, Hsiao H-Y, Cheng T-J, Chen RL (2008) Assays for serum cholinesterase activity by capillary electrophoresis and an amperometric flow injection choline biosensor. Anal Chim Acta 623:157–162CrossRefGoogle Scholar
  16. Jia ZJ, Fang Q, Fang ZL (2004) Bonding of glass microfluidic chips at room temperatures. Anal Chem 76:5597–5602CrossRefGoogle Scholar
  17. Li X, Tian J, Nguyen T, Shen W (2008) Paper-based microfluidic devices by plasma treatment. Anal Chem 80:9131–9134CrossRefGoogle Scholar
  18. Li X, Tian J, Garnier G, Shen W (2010) Fabrication of paper-based microfluidic sensors by printing. Colloids Surf B Biointerfaces 76:564–570CrossRefGoogle Scholar
  19. Li X, Ballerini DR, Shen W (2012) A perspective on paper-based microfluidics: current status and future trends. Biomicrofluidics 6:11301–1130113CrossRefGoogle Scholar
  20. Lin CH, Lee GB, Lin YH, Chang GL (2001) A fast prototyping process for fabrication of microfluidic systems on soda-lime glass. J Micromech Microeng 11:726–732CrossRefGoogle Scholar
  21. Lin CH, Tsai CH, Fu LM (2005) A rapid three-dimensional vortex micromixer utilizing self-rotation effects under low Reynolds number conditions. J Micromech Microeng 15:935–943CrossRefGoogle Scholar
  22. Liu X, Cheng C, Martinez A, Mirica K, Li X, Phillips S, Mascarenas M, Whitesides G et al (2011) A portable microfluidic paper-based device for ELISA. In: Proceedings of the IEEE 24th international conference on microelectromechanical systems (MEMS 2011), pp 75–78Google Scholar
  23. Lu KY, Wo AM, Lo YJ, Chen KC, Lin CM, Yang CR (2006) Three dimensional electrode array for cell lysis via electroporation. Biosens Bioelectron 22:568–574CrossRefGoogle Scholar
  24. Manerba A, Lombardi C, Vizzardi E, Maiandi C, Milesi G, Bugatti S, Bettari L, Romeo A, Metra M, Cas LD (2010) Role of blood urea nitrogen variations in patients with chronic heart failure. Eur Heart J 31:1053–1054Google 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 46:1318–1320CrossRefGoogle Scholar
  26. Martinez AW, Phillips ST, Nie ZH, Cheng CM, Carrilho E, Wiley BJ, Whitesides GM (2010) Programmable diagnostic devices made from paper and tape. Lab Chip 10:2499–2504CrossRefGoogle Scholar
  27. McCormick RM, Nelson RJ, Alonso-Amigo MG, Benvegnu DJ, Hooper HH (1997) Microchannel electrophoretic separations of DNA in injection-molded plastic substrates. Anal Chem 69:2626–2630CrossRefGoogle Scholar
  28. Meulemans A, Delsenne F (1994) Measurement of nitrite and nitrate levels in biological samples by capillary electrophoresis. J Chromatogr B Biomed Sci Appl 660:401–404CrossRefGoogle Scholar
  29. Pumera M, Wang J, Opekar F, Jelinek I, Feldman J, Lowe H, Hardt S (2002) Contactless conductivity detector for microchip capillary electrophoresis. Anal Chem 74:1968–1971CrossRefGoogle Scholar
  30. Reches M, Mirica KA, Dasgupta R, Dickey MD, Butte MJ, Whitesides GM (2010) Thread as a matrix for biomedical assays. ACS Appl Mater Interfaces 2:1722–1728CrossRefGoogle Scholar
  31. Ruecha N, Siangproh W, Chailapakul O (2011) A fast and highly sensitive detection of cholesterol using polymer microfluidic devices and amperometric system. Talanta 84:1323–1328CrossRefGoogle Scholar
  32. Schuchert-Shi A, Hauser PC (2008) Monitoring the enzymatic conversion of urea to ammonium by conventional or microchip capillary electrophoresis with contactless conductivity detection. Anal Biochem 376:262–267CrossRefGoogle Scholar
  33. Wan QJ, Kuban P, Tanyanyiwa J, Rainelli A, Hauser PC (2004) Determination of major inorganic ions in blood serum and urine by capillary electrophoresis with contactless conductivity detection. Anal Chim Acta 525:11–16CrossRefGoogle Scholar
  34. Wei YC, Lin CH, Wang YN, Fu LM (2012) Capillary electrophoresis electrochemical (CE–EC) detection on a novel thread-based microfluidic device with 3D sensing electrodes. In: Proceedings of the IEEE 6th international conference on nano/molecular medicine and engineering (NANOMED 2012), pp 101–105Google Scholar
  35. Wei Y-C, Fu L-M, Lin C-H (2013) Electrophoresis separation and electrochemical detection on a novel thread-based microfluidic device. Microfluid Nanofluid 14:583–590CrossRefGoogle Scholar
  36. Wilke R, Buttgenbach S (2003) A micromachined capillary electrophoresis chip with fully integrated electrodes for separation and electrochemical detection. Biosens Bioelectron 19:149–153CrossRefGoogle Scholar
  37. Woolley AT, Mathies RA (1995) Ultra-high-speed DNA sequencing using capillary electrophoresis chips. Anal Chem 67:3676–3680CrossRefGoogle Scholar
  38. You H, Matsuzuka N, Yamaji T, Tabata O (2000) Deep X-ray exposure system with multistage for 3D microfabrication. In: Proceedings of the international symposium on micromechatronics and human science (MHS 2000), pp 53–58Google Scholar
  39. Zeng Y, Chen H, Pang DW, Wang ZL, Cheng JK (2002) Microchip capillary electrophoresis with electrochemical detection. Anal Chem 74:2441–2445CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Department of Mechanical and Electro-Mechanical EngineeringNational Sun Yat-sen UniversityKaohsiungTaiwan, ROC

Personalised recommendations