Biosensors and Bioelectronics 21 (2005) 79–86 Quartz crystal microbalance-with dissipation monitoring (QCM-D) for real time measurements of blood coagulation density and immune complement activation on artificial surfaces Marcus Andersson a,∗ , Jonas Andersson b , Anders Sellborn a , Mattias Berglin a , Bo Nilsson b , Hans Elwing a a Department of Cell and Molecular Biology/Interface Biophysics Lundberg Laboratory, G¨ oteborg University, Box 462, SE-405 30 G¨ oteborg, Sweden b Department of Oncology, Radiology and Clinical Immunology, Section of Clinical Immunology, Rudbeck Laboratory C5, Uppsala University Hospital, SE-751 85 Uppsala, Sweden Received 24 June 2004; received in revised form 24 September 2004; accepted 29 September 2004 Available online 11 November 2004 Abstract A recently developed variant of quartz crystal microbalance (QCM) called QCM-with dissipation monitoring (QCM-D) allows simultaneous and simple measurements of changes in adsorbed mass as well as the viscoelastic property (D-factor) of deposited protein layers on the sensor surface. We have taken the QCM-D technology a step further and demonstrated its advantages in the study of protein assembly as a consequence of surface induced immune complement activation, or contact activated blood coagulation. In the present study we have continued our QCM- D investigations of surface assembly of fibrin clot formation and complement activation and incubated differently modified quartz sensor surfaces in blood plasma and sera. Polymer surfaces used were spin-coated polyethylene, poly(ethylene terephtalate), poly(methylmetacrylate) and poly(dimethylsiloxane). Also used were sputtered titanium and heparin grafted surfaces. In this investigation we found that we could describe the surface induced coagulation with four independent parameters: (1) Time of onset of coagulation, (2) fibrin deposition rate, (3) total frequency shift at stable plateau, and (4) fibrin clot density. The most important finding was that the blood plasma clot density can be assessed with the use of D determinations and that the clot density varied significantly with the chemical composition of the surface. However, the D-factor did not give any new analytical information about the possible complement activation mechanisms. Nevertheless, the QCM-D was found to be a reliable tool for the analysis of surface induced complement activation. We also compared the QCM-D technique with traditional enzyme immuno assay (EIA) measurements of soluble products from the surface activation of the complement and coagulation systems. We found that the results from EIA and QCM-D measurements corresponded well for the complement activation but not for the coagulation, probably due to the biological complexity of the coagulation system. © 2004 Elsevier B.V. All rights reserved. Keywords: Quartz crystal microbalance; Blood coagulation; Complement activation; Enzyme immuno assay 1. Introduction Quartz crystal microbalance (QCM) is a high frequency surface sensitive method for various biosensor applications (Marx, 2003). Most applications monitor only changes of resonant frequency (f) of the adsorbed layers on the sensor ∗ Corresponding author. Tel.: +46 31 7732566; fax: +46 31 7732599. E-mail address: marcus.andersson@gmm.gu.se (M. Andersson). surfaces. Recently, a variation of QCM has been developed which simultaneously allows registration of dissipation (D) of the sensor signal (Rodahl et al., 1995; Hook et al., 1998). The D-factor is related to the viscoelastic properties of the ad- sorbed layer. The new QCM modification, called QCM with dissipation monitoring or QCM-D, has greatly increased the analytical range of the instrument in different applications, for example in studies of single protein adsorption (Hook et al., 1998) and adsorption of phospholipid layers (Glasmastar 0956-5663/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.bios.2004.09.026