Blood coagulation time measurements using 400 MHz thickness mode resonator

Abstract

This thesis presents a novel blood coagulation time measurement methodology which requires as low as 1 L of whole blood. The method performs measurements using whole blood without plasma separation. In this regard, the whole blood sample is placed on the top surface of a fused quartz plate (glass substrate) where an ultrasonic transducer (operating in thickness mode) is fabricated on the bottom surface. The transducer utilizes a short burst of 400 MHz compressional acoustic waves along the thickness of glass substrate. The location of the blood sample is aligned with the transducer; therefore, the re ected acoustic waves from the blood/quartz interface are captured and converted to electrical signals by the transducer. A Mason modeling of the transducer in frequency domain was expressed to show the changes of resonance frequency of the transducer for di erent samples, like air, water, and blood, alongside with a numerical modeling to show amplitude of acoustic waves propagating inside the transducer in time domain. The acoustic impedance of the blood changes due to the coagulation process. This a ects the re ection coe cient and amplitude of the re ected waves from the blood/quartz interface. A theoretical model was developed to show dependency of the acoustic waves amplitude to the re ection coe cient. Thus, the blood coagulation time was determined by monitoring the re ected acoustic waves amplitude. The transducer was made of 8 m thick of sputtered Zinc Oxide (ZnO) thin- lm that is operating at approximately 400 MHz TE (Thickness Extensional) mode. In the experiments, whole blood sample was used without any preparation. The method was tested using citrated blood with calcium chloride and activated partial thromboplastin (aPTT) reagents. We observed that aPTT coagulation times lengthen from 25 sec. to 47 sec. with the addition of heparin. The proposed method has a potential to be used in a disposable low cost portable coagulation time measurement cartridge for patient self-testing. The measurements were performed by collecting the amplitude of the re ected waves versus the time at speci c frequency (400 MHz); however, another possible way could be using a simple oscillator and a digital counter to track the resonance frequency and quality factor of the transducer versus the time. This will further reduce the cost and size of the proposed method. Nevertheless, this transducer has a potential to be used for characterizing liquid samples parameters like viscosity, if it is operated in frequency domain and the input impedance is being tracked. This could be used for the applications where the lower volume of an expensive drug or chemical to be tested, is mostly desired.

Bu tez, yeni bir kan p ht la sma s uresi ol c um metodolojisi sunmaktad r. Metod plazma ayr m olmaks z n 1 mikro L tam kan gerektirir. Bu tu n kan orneg` i, ultrasonik gu c cevirici (kal nl k modunda cal san) ile birle stirilmi s bir kuvars plakan n ust y uzeyine yerle stirilir (cam alt tabaka). D on u st ur uc u 400MHz'lik k sa bir sinus dalgalar uretir. Bu dalgalar cam alt tabakan n kal nl g boyunca akustik dalga olarak yay l r. Kan n yeri ornek d on u st ur uc u ile hizalanm st r; Kan/kuvars yuzeyinden yans yan dalgalar yeniden d on u st ur uc uz u taraf ndan toplan r ve elektiksel sinyallere cevirilir. Bu tezden d on u st ur uc u frekans alannda Mason modellemesi ile ifade edildi. Farkl o rnekler i cin transdu serin rezonans frekans ndaki deg` i simleri incelendi, hava, su ve kan gibi malzemelerden gelen yansilmalar zaman alan nda hesapland . Kan n akustik empedans , p ht la sma su recine bag` l olarak deg` i sir. Bu Yans yan dalgalar n faz n ve genli gini de gi stiri. De gi sim hesaplanmas i cin teorik bir model geli stirildi. B oylece kan p ht la smas akustik dalgalar n izlenmesiyle ol culebilir. Transdu ser, 8 mikro- metre kal nl g` nda pu sku rtu lmu s C inko Oksit'ten (ZnO) yap lm st r. Yakla s k 400 MHz TE (Kal nl k Uzama) modunda cal s r. Deneylerde, tam kan o rneg` i herhangi bir ornek haz rlama basamagi olmaks z n kullan ld . Y ontem kalsiyum klor ur ile sitratlanm s kan ve tromboplastin (aPTT) reakti eri kullan larak test edildi. Heparin ilavesi ile aPTT p ht la sma s urelerinin 25 saniyeden 47 saniyeye uzad g` n go zlemlendi. O nerilen yo ntem Tek kullan ml k du su k maliyetli ta s nabilir p ht la sma s uresi ol c um unde kullan labilir. P ht la sma zaman rezonans frekan ve kalite izlemek gibi yontemlerle de ol c ulebilir. P ht la sma zamani yan nda onerilen metod s v lar n karakterizasyonu i cn de kullan labilir.