title: High sensitivity micro-elastometry: applications in blood coagulopathy.
abstract: Highly sensitive methods for the assessment of clot structure can aid in our understanding of coagulation disorders and their risk factors. Rapid and simple clot diagnostic systems are also needed for directing treatment in a broad spectrum of cardiovascular diseases. Here we demonstrate a method for micro-elastometry, named resonant acoustic spectroscopy with optical vibrometry (RASOV), which measures the clot elastic modulus (CEM) from the intrinsic resonant frequency of a clot inside a microwell. We observed a high correlation between the CEM of human blood measured by RASOV and a commercial thromboelastograph (TEG), (R = 0.966). Unlike TEG, RASOV requires only 150 μL of sample and offers improved repeatability. Since CEM is known to primarily depend upon fibrin content and network structure, we investigated the CEM of purified clots formed with varying amounts of fibrinogen and thrombin. We found that RASOV was sensitive to changes of fibrinogen content (0.5-6 mg/mL), as well as to the amount of fibrinogen converted to fibrin during clot formation. We then simulated plasma hypercoagulability via hyperfibrinogenemia by spiking whole blood to 150 and 200% of normal fibrinogen levels, and subsequently found that RASOV could detect hyperfibrinogenemia-induced changes in CEM and distinguish these conditions from normal blood.
authors: Department of Physics and Astronomy, University of North Carolina at Chapel Hill, CB 3255, Chapel Hill, NC 27599, USA.
authors: Gongting
authors: G
authors: Wu
authors: Charles R
authors: CR
authors: Krebs
authors: Feng-Chang
authors: FC
authors: Lin
authors: Alisa S
authors: AS
authors: Wolberg
authors: Amy L
authors: AL
authors: Oldenburg
mesh_terms: D001777:Blood Coagulation; D001778:Blood Coagulation Disorders / Q000097:blood*; D001780:Blood Coagulation Tests / Q000295:instrumentation / Q000379:methods; D055119:Elastic Modulus; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D012680:Sensitivity and Specificity
chemical_list: D005337:Fibrin; D005340:Fibrinogen
references: J Appl Physiol (1985). 1987 Sep;63(3):1003-7
references: 3654450
references: Phys Med Biol. 2010 Feb 21;55(4):1189-201
references: 20124653
references: Arterioscler Thromb Vasc Biol. 2005 Oct;25(10):2228-33
references: 16123313
references: Diabet Med. 2002 Oct;19(10):862-6
references: 12358876
references: IEEE J Sel Top Quantum Electron. 2011 Jul 21;18(3):1100-1109
references: 23833549
references: Science. 2009 Aug 7;325(5941):741-4
references: 19661428
references: Proc SPIE Int Soc Opt Eng. 2012;8214:82140G
references: 22506093
references: J Biomech Eng. 1999 Apr;121(2):184-7
references: 10211452
references: PLoS One. 2012;7(8):e41966
references: 22870270
references: Biophys Chem. 1981 Feb;13(1):15-23
references: 7260325
references: Phys Rev Lett. 1995 Dec 11;75(24):4425-4428
references: 10059905
references: Pediatr Rheumatol Online J. 2011 Mar 25;9:8
references: 21439056
references: Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9133-7
references: 15967976
references: Blood Coagul Fibrinolysis. 1995 Feb;6(1):79-86
references: 7795157
references: Biophys J. 1999 Nov;77(5):2813-26
references: 10545379
references: Blood. 2011 May 5;117(18):4953-63
references: 21355090
references: Clin Lab Haematol. 2005 Apr;27(2):81-90
references: 15784122
references: Thromb Haemost. 1996 Oct;76(4):535-40
references: 8902992
references: Blood. 2009 Nov 5;114(19):3994-4001
references: 19687509
references: Anesthesiology. 2000 May;92(5):1223-5
references: 10781265
references: Blood Coagul Fibrinolysis. 1994 Oct;5(5):719-23
references: 7865677
references: Adv Protein Chem. 2005;70:247-99
references: 15837518
references: Blood Coagul Fibrinolysis. 2008 Dec;19(8):765-70
references: 19002042
references: Biophys J. 2010 Oct 6;99(7):2374-83
references: 20923673