Quartz crystal microbalance-with dissipation monitoring (QCM-D) for real time measurements of blood coagulation density and immune complement activation on artificial surfaces.

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.

[1]  H. Elwing,et al.  Complement activation and inflammation triggered by model biomaterial surfaces. , 1998, Journal of biomedical materials research.

[2]  J. A. Engels,et al.  In situ complement activation by polyethylene wear debris. , 2001, Journal of biomedical materials research.

[3]  G. Elgue,et al.  Measuring the degree of plasma contact activation induced by artificial materials. , 2002, Thrombosis research.

[4]  B. Kasemo,et al.  Energy Dissipation Kinetics for Protein and Antibody−Antigen Adsorption under Shear Oscillation on a Quartz Crystal Microbalance , 1998 .

[5]  B. Nilsson,et al.  Titanium Is a Highly Thrombogenic Biomaterial: Possible Implications for Osteogenesis , 1999, Thrombosis and Haemostasis.

[6]  I Lundström,et al.  Comparison of surface plasmon resonance and quartz crystal microbalance in the study of whole blood and plasma coagulation. , 2000, Biosensors & bioelectronics.

[7]  B. Kasemo,et al.  Variations in coupled water, viscoelastic properties, and film thickness of a Mefp-1 protein film during adsorption and cross-linking: a quartz crystal microbalance with dissipation monitoring, ellipsometry, and surface plasmon resonance study. , 2001, Analytical chemistry.

[8]  G. Sauerbrey,et al.  Use of quartz vibration for weighing thin films on a microbalance , 1959 .

[9]  P. Tengvall,et al.  Inflammatory cell recruitment, distribution, and chemiluminescence response at IgG precoated- and thiol functionalized gold surfaces. , 1999, Journal of biomedical materials research.

[10]  B. Nilsson,et al.  A simplified assay for the detection of C3a in human plasma employing a monoclonal antibody raised against denatured C3. , 1988, Journal of immunological methods.

[11]  Fredrik Höök,et al.  Quartz crystal microbalance setup for frequency and Q‐factor measurements in gaseous and liquid environments , 1995 .

[12]  Marcus Andersson,et al.  Methods for research on immune complement activation on modified sensor surfaces , 2003 .

[13]  V. V. van Hinsbergh,et al.  Aberrant fibrin formation and cross-linking of fibrinogen Nieuwegein, a variant with a shortened Aalpha-chain, alters endothelial capillary tube formation. , 2001, Blood.

[14]  K. Marx,et al.  Quartz crystal microbalance: a useful tool for studying thin polymer films and complex biomolecular systems at the solution-surface interface. , 2003, Biomacromolecules.

[15]  Fredrik Höök,et al.  Protein adsorption on supported phospholipid bilayers. , 2002, Journal of colloid and interface science.

[16]  H. Elwing,et al.  The effect of substrate molecular mobility on surface induced immune complement activation and blood plasma coagulation. , 2004, Biomaterials.

[17]  Ernesto Occhiello,et al.  Polymer Surfaces: From Physics to Technology , 1994 .

[18]  B. Nilsson,et al.  Contact between a polymer and whole blood: sequence of events leading to thrombin generation. , 2001, The Journal of laboratory and clinical medicine.

[19]  C. Dahlgren,et al.  Phagocytosis and hydrophobicity: a method of calculating contact angles based on the diameter of sessile drops. , 1981, Journal of immunological methods.

[20]  P. Tengvall,et al.  Blood protein interactions with titanium surfaces. , 1996, Journal of biomaterials science. Polymer edition.

[21]  B. Nilsson,et al.  A new in vitro model to study interaction between whole blood and biomaterials. Studies of platelet and coagulation activation and the effect of aspirin. , 1999, Biomaterials.

[22]  A. Larsson,et al.  Heparin coating of the stent : graft effects on platelets, coagulation and complement activation , 2001 .

[23]  A. Bengtsson,et al.  Extracorporeal (“ex vivo”) connection of pig kidneys to humans. III. Studies of plasma complement activation and complement deposition in the kidney tissue , 1998, Xenotransplantation.

[24]  G. Sauerbrey.  Verwendung von Schwingquarzen zur Wägung dünner Schichten und zur Mikrowägung , 1959 .

[25]  S. Frøland,et al.  Quantification of the Terminal Complement Complex in Human Plasma by an Enzyme‐Linked Immunosorbent Assay Based on Monoclonal Antibodies against a Neoantigen of the Complex , 1985, Scandinavian journal of immunology.

[26]  M. V. Voinova,et al.  Viscoelastic Acoustic Response of Layered Polymer Films at Fluid-Solid Interfaces: Continuum Mechanics Approach , 1998, cond-mat/9805266.

[27]  V. Videm,et al.  A novel enzyme immunoassay for plasma thrombospondin. Comparison with beta-thromboglobulin as platelet activation marker in vitro and in vivo. , 2000, Thrombosis research.

[28]  M. Blombäck,et al.  Altered properties of the fibrin gel structure in patients with IDDM , 1996, Diabetologia.

[29]  Marcus Andersson,et al.  Acoustics of blood plasma on solid surfaces , 2002, Journal of biomaterials science. Polymer edition.

[30]  Ingemar Lundström,et al.  Surface plasmon resonance and free oscillation rheometry in combination: a useful approach for studies on haemostasis and interactions between whole blood and artificial surfaces. , 2002, Biosensors & bioelectronics.

[31]  B Liedberg,et al.  Blood plasma coagulation studied by surface plasmon resonance. , 2000, Journal of biomedical optics.

[32]  I. Lundström,et al.  Complement deposition from human sera on silicon surfaces studied in situ by ellipsometry. The influence of surface wettability. , 1986, European journal of biochemistry.