A quartz crystal microbalance (QCM) biosensor with nanogram sensitivity has been constructed through a reasonable designing and biological processing of the piezoelectric quartz crystals. Due to its highly sensitivity, real time detection and low cost, the proposed QCM biosensor has a promising potential in blood coagulation research. In the current study, the QCM biosensor was used to determine the activated partial thromboplastin time (APTT) for 120 anticoagulated plasma specimens. A good linear relationship was found in a double-logarithmic plot of APTT versus fibrinogen concentration in the range of 1.58–6.30 g/L. For factor VIII, the detection range by the QCM biosensor is 0.0185–0.111 mg/L. The QCM biosensor results were compared with those obtained by commercial optical coagulometry and a good agreement (correlation coefficient is 0.949 for fibrinogen, and 0.948 for factor VIII) was reached. Furthermore, the QCM determination can be completed within 10 min. Our study suggested that the proposed QCM biosensor could provide for more convenient and time saving operations, which may be useful in clinical situations for rapid monitoring of anticoagulant therapy using small volume (20 μL) plasma specimens.
References
[1]
Li, G.; Shi, X.; Yang, P.; Zhao, A.; Huang, N. Investigation of fibrinogen adsorption on solid surface by quartz crystal microbalance with dissipation (QCM-D) and ELISA. Solid State Ionics 2008, 179, 932–935.
[2]
White, G.C.; Shoemaker, C.B. Factor VIII gene and hemophilia A. Blood 1989, 73, 1–12.
[3]
Chen, C.; Fang, X.D.; Zhu, J.; Wu, X.F.; Zhang, Z.C.; Gu, J.X.; Wang, Z.Y.; Chi, C.W. The gene expression of coagulation factor VIII in mammalian cell lines. Thromb. Res. 1999, 95, 105–115.
[4]
Schambeck, C.M.; Grossmann, R.; Zonnur, S.; Berger, M.; Teuchert, K.; Spahn, A.; Walter, U. High factor VIII (FVIII) levels in venous thromboembolism: Role of unbound FVIII. Thromb. Haemost 2004, 92, 42–46.
[5]
Martinelli, I.; Primignani, M.; Aghemo, A.; Reati, R.; Bucciarelli, P.; Fabris, F.; Battaglioli, T.; Dell'Era, A.; Mannucci, P.M. High levels of factor VIII and risk of extra-hepatic portal vein obstruction. J. Hepatol. 2009, 50, 916–922.
[6]
Tatsumi, K.; Ohashi., K.; Taminishi, S.; Sakurai, Y.; Ogiwara, K.; Yoshioka, A.; Okano, T.; Shima, M. Regulation of coagulation factors during liver regeneration in mice: Mechanism of factor VIII elevation in plasma. Thromb. Res. 2011, 128, 54–61.
[7]
Anand, S.S.; Yusuf, S.; Pogue, J.; Ginsberg, J.S.; Hirsh, J. Relationship of activated partial thromboplastin time to coronary events and bleeding in patients with acute coronary syndromes who receive heparin. Circulation 2003, 107, 2884–2888.
[8]
Sanchez, J.; Lundquist, P.B.; Elgue, G.; Larsson, R.; Olsson, P. Measuring the degree of plasma contact activation induced by artificial materials. Thromb. Res. 2002, 105, 407–412.
[9]
Andersson, M.; Sellborn, A.; Fant, C.; Gretzer, C.; Elwing, H. Acoustics of blood plasma on solid surfaces. J. Biomater. Sci. Polym. Ed. 2002, 13, 907–917.
Vikinge, T.P.; Hansson, K.M.; Benesch, J.; Johansen, K.; Ranby, M.; Lindahl, T.L.; Liedberg, B.; Lundstom, I.; Tengvall, P. Blood plasma coagulation studied by surface plasmon resonance. J. Biomed. Opt. 2000, 5, 51–55.
[12]
Vikinge, T.P.; Hansson, K.M.; Sandstrom, P.; Liedberg, B.; Lindahl, T.L.; Lundstrom, I.; Tengvall, P.; Hook, F. Comparison of surface plasmon resonance and quartz crystal microbalance in the study of whole blood and plasma coagulation. Biosens. Bioelectron. 2000, 15, 605–613.
[13]
Hansson, K.M.; Tengvall, P.; Lundstrom, I.; Ranby, M.; Lindahl, T.L. Surface plasmon resonance and free oscillation rheometry in combination: A useful approach for studies on haemostasis and interactions between whole blood and artificial surfaces. Biosens. Bioelectron. 2002, 17, 747–759.
[14]
Evans, P.A.; Hawkins, K.; Lawrence, M.; Williams, R.L.; Barrow, M.S.; Thirumalai, N.; Williams, P.R. Rheometry and associated techniques for blood coagulation studies. Med. Eng. Phys. 2008, 30, 671–679.
[15]
Lin, T.M.; Cheng, T.J.; Wu, T.H.; Chang, H.C. Comparing a piezoelectric quartz crystal with an optical coagulometer in monitoring high-dose heparin therapy by determining whole blood activated partial thromboplastin time and activated clotting time. Sens. Actuators B Chem. 2005, 109, 270–277.
[16]
Andersson, M.; Andersson, J.; Sellborn, A.; Berglin, M.; Nilsson, B.; Elwing, H. Quartz crystal microbalance-with dissipation monitoring (QCM-D) for real time measurements of blood coagulation density and immune complement activation on artificial surfaces. Biosens. Bioelectron. 2005, 21, 79–86.
[17]
Jung, H.; Tae, G.; Kim, Y.H.; Johannsmann, D. Change of viscoelastic property and morphology of fibrin affected by antithrombin III and heparin: QCM-Z and AFM study. Colloid. Surf. B Biointerfaces 2009, 68, 111–119.
[18]
Aizawa, H.; Kurosawa, S.; Tozuka, M.; Park, J.W.; Kobayashi, K.; Tanaka, H. Conventional detection method of fibrinogen and fibrin degradation products using latex piezoelectric immunoassay. Biosens. Bioelectron. 2003, 18, 765–771.
[19]
Aizawa, H.; Kurosawa, S.; Tozuka, M.; Park, J.W.; Kobayashi, K. Rapid detection of fibrinogen and fibrin degradation products using a smart QCM-sensor. Sens. Actuators B Chem. 2004, 101, 150–154.
[20]
Muramatsu, H.; Kimura, K.; Ataka, T.; Homma, R.; Miura, Y.; Karube, I. A quartz crystal viscosity sensor for monitoring coagulation reaction and its application to a multichannel coagulation detector. Biosens. Bioelectron. 1991, 6, 353–358.
[21]
Cheng, T.J.; Chang, H.C.; Lin, T.M. A piezoelectric quartz crystal sensor for the determination of coagulation time in plasma and whole blood. Biosens. Bioelectron. 1998, 13, 147–156.
[22]
Chang, H.C.; Cheng, T.J.; Wu, T.H.; Lin, T.M. Detection of coagulation time in whole blood containing anticoagulant by piezoelectric quartz crystal sensor. Sens. Actuators B Chem. 2000, 66, 296–298.
[23]
Cheng, T.J.; Lin, T.M.; Wu, T.H.; Chang, H.C. Determination of heparin levels in blood with activated partial thromboplastin time by a piezoelectric quartz crystal sensor. Anal. Chim. Acta 2001, 432, 101–111.
[24]
Wang, Y.; Chen, M.; Zhang, L.; Ding, Y.; Luo, Y.; Xu, Q.; Shi, J.; Cao, L.; Fu, W. Rapid detection of human papilloma virus using a novel leaky surface acoustic wave peptide nucleic acid biosensor. Biosens. Bioelectron. 2009, 24, 3455–3460.
[25]
Yao, C.; Zhu, T.; Tang, J.; Wu, R.; Chen, Q.; Chen, M.; Zhang, B.; Huang, J.; Fu, W. Hybridization assay of hepatitis B virus by QCM peptide nucleic acid biosensor. Biosens. Bioelectron. 2008, 23, 879–885.
[26]
Kanahara, M.; Kai, H.; Okamura, T.; Wada, T.; Suda, K.; Imaizumi, T.; Sagawa, K. Usefulness of high-concentration calcium chloride solution for correction of activated partial thromboplastin time (APTT) in patients with high-hematocrit value. Thromb. Res. 2008, 121, 781–785.
