生物流变特性测试方法及应用研究
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摘要
流变学是研究非牛顿流体在应力、应变、温度等条件下与时间因素有关的变形和流动的科学，是介于物理、力学、医学、生物和工程技术之间的一门边缘交叉学科。在自然界和工程技术界，粘弹性流体、粘塑性流体、血液以及绝大多数生物流体的流动都呈现出非牛顿流体性态，非牛顿流体的流变性质、流体流动与变形的力学分析、流体的本构方程、物质参数与函数的测量、流体粘温性能、流动曲线、凝固性、粘弹性、触变性等一系列流变学特性指标的测试丞待解决。尤其在生物流变学领域，血液流动动力学，血液细胞的变形规律，血液和其他体液、各种软、硬组织的力学性能，各种生物流体的流变特性与疾病的关系等生物流变学特性测试问题被相继提出，血液流变学、细胞流变学以及血液凝固过程中的流变机理和参数测量已经成为研究热点。本论文围绕“血液流变、细胞流变以及血液凝固过程中的流变特性测试方法”等科研项目，开展生物流变学特性测试方法与系统应用研究。
论文首先全面综述了流变学的国内外研究现状，阐述了非牛顿流体流变学研究领域的分类及研究的重要意义，详细分析了血液流变学、细胞流变学、血液凝固过程中的流变机理和参数测量等生物流变学特性测试的研究内容，阐明了生物流变学与心脑血管疾病、恶性肿瘤及糖尿病等多种疾病的关系以及生物流变学在血液流动状态下对止血、凝血及血栓形成中的生理、病理作用及临床意义。
其次以流变学的研究对象和研究方法为基础，全面阐述了非牛顿流体流变学测量理论，对非牛顿流体流动与变形进行了力学分析，推导出非牛顿流体流动的基本微分方程，构建了纯粘性非牛顿流体的本构方程，分析了非牛顿流体的典型流动以及流体粘弹性与触变性等流变性质，重点研究了稳态剪切流场的主要流变学参数和小振幅振荡流场与流体粘弹性的流变学参数表征方法。
针对生物流变学特性测试研究，提出了稳态剪切速度衰减血流变测试方法、基于激光衍射和散射技术的细胞形态、变形与聚集等细胞流变学特性测试方法以及基于小振幅振荡流场的双磁路磁珠振荡法、光学散射测量法和发色底物测量法的等血液凝固过程中的流变特性测试方法，解决了生物流变学领域的血液流动性、细胞变形性、细胞聚集性以及血液凝固性等一系列生物流体流变学特性测试技术与方法。
提出了基于稳态剪切流场、拉伸流场和小振幅振荡流场的生物流变学特性测试特性模型，建立了高灵敏度、高可靠性的库特式生物流体流变学特性测试系统和动态数据建模平台，采用应力驱动、实时频率扫描、小振幅振荡和强迫振荡四种模式实现生物流体流变学特性测试及动态数据建模。
论文对提出的稳态剪切速度衰减血流变测试方法和激光衍射细胞流变学特性测试方法进行了实验验证，针对目前非牛顿流体流变特性测试仪器无法标定以及测试结果无法溯源等问题，研制了一种稳定可靠的非牛顿流体标准物质，提出了非牛顿流体标定方法。
完成了基于稳态剪切速度衰减测试方法的血流变测试系统应用研究。系统采用提出的速度衰减法锥板测试技术实现全量程、逐点扫描、快速、稳态的血流变特性测量，具有自动加样、自动混匀、自动测试、自动清洗、液面感应等先进功能，具有非牛顿流体标准物质标定和校准功能。
完成了基于双磁路小振幅振荡测试方法的凝血测试系统应用研究。利用提出的双磁路磁珠振荡法测量原理实现血液凝固过程中的流变特性功能测试。系统具有先进的三维空间加样系统、驱动器内置点到点功能、S曲线加速、直线/圆弧插补运动功能以及微弱信号采集放大功能。系统具有功能强大、实时多任务操作、检测速度快、精度高等特点。
本论文的研究为生物流变学特性测试方法及应用奠定了必要的理论基础，对于推动我国生物流变学特性测试技术研究有着重要的指导意义。
Rheology is a science that studies the time-related deformation and flow ofnon-Newtonian fluids under the conditions of stress, strain, and temperature. It is aninterdisciplinary subject which includes some parts of physics, mechanics, medicine,biology, and engineering. The flow of viscoelastic fluids, viscoplastic fluids, bloods,and most of biofluids demonstrates the characteristics of non-Newtonian fluid. Thetesting of some rheological characteristics, such as the rheological characteristics ofnon-Newtonian fluids, mechanical analysis of fluid flow and deformation,constitutive equations of fluids, parameters and functions of material,viscosity-temperature characteristics of fluids, flow curve, coagulability,viscoelasticity, and thixotropy, demands prompt solution. Especially in the field ofbiomedical engineering, the test problems about the biorheological characteristics,such as the dynamics of blood flow, deformation laws of blood cell, mechanicalproperts of blood, other body fluids, and all kinds of soft and hard tissues, andrelations between the rheological characteristics of biofluids and illnesses, are raisedin succession. Hemorheology, cell rheology, and the rheological mechanism andparameter measurement during the process of blood coagulation, have attractedmany researcher’s attention. This thesis focuses on the research on thebiorheological characteristic testing method and its applications, along with theresearch project Rheological Characteristic Testing Methods in Hemorheology, CellRheology, and the Process of Blood Coagulation.
An overall review of the rheology is given. The classification and researchsignificance of the non-Newtonian fluid rheology are introduced. Research topics ofthe biorheological characteristic testing, such as the hemorheology, cell rheology,and the rheological mechanism and parameter measurement during the process ofblood coagulation, are analyzed in detail. The relations between the biorheology andsome illnesses such as cardiovascular and cerebrovascular disease, malignant tumor,and diabetes, are revealed. The physiological and pathological actions of thebiorheology towards the hemostasis, blood coagulation, and formation of thrombuswhile the blood flows are discussed.
Based on the research object and method of rheology, the measurement theory of non-Newtonian fluid rheology is introduced. The mechanical characteristics of thenon-Newtonian fluid deformation and flow are analyzed. Basic differentialequations of the non-Newtonian fluid flow are deduced. Constitutive equations ofthe pure viscous non-Newtonian fluids are built. Some typical flows ofnon-Newtonian fluid, and rheological characteristics such as viscoelasticity andthixotropy, are analyzed. The main rheological parameters of the steady state shearflow field and the rheological parameter characterization methods of the smallamplitude oscillatory flow field and fluid viscoelasticity are studied.
According to the research on the biorheological characteristic testing technique, ahemorheological test method based on steady state shear velocity attenuationmethod is presented. A test method of cell rheological characteristic, such as cellmorpha, deformation and aggregation, based on the technique of laser diffractionand scattering is proposed. Rheological characteristic test methods during theprocess of blood coagulation, such as double magnetic circuits magnetic beadoscillatory method, optical scattering measuring method and chromogenic substratemeasuring method, based on the small-amplitude oscillatory flow field, are alsodemonstrated. The problems of some test techniques and methods of biorheologicalcharacteristic, such as the blood flow, cell deformation, cell aggregation and bloodcoagulation, are resolved.
Biorheological characteristic test models are given based on steady state shearflow field, elongational flow field, and small-amplitude oscillatory flow field. Ahighly sensitive and reliable Couette biofluid rheological characteristic test systemand dynamic data modeling system are built. The biofluid rheological characteristictest and dynamic data modeling are accomplished by using the models of stressdriving, real-time frequency sweep, small amplitude oscillation, and forcedoscillation.
Experiments are conducted to verify the proposed hemorheological test methodbased on steady state shear velocity attenuation method and cell rheological testmethod based on laser diffraction method. To sovle the problems that theinstruments for non-Newtonian fluid rheological characteristic testing cannot becalibrated and its testing results cannot be traced, a kind of stable and reliablenon-Newtonian fluid standard substance is developed and a non-Newtonian fluidcalibration method is proposed.
The application research on hemorheological test system based on steady stateshear velocity attenuation method is completed. The system realizes the full-range,point-by-point scanning, rapid and steady-state measurement of the hemorheologicalcharacteristics using the proposed velocity attenuation cone-plate testing method.The system has some advanced functions such as automatic sampling, blending,testing, and cleaning, together with the function of liquid level detecting. It also hasthe functions of non-Newtonian fluid standard substance calibration and adjustment.
The application research on blood coagulation test system based on doublemagnetic circuit small amplitude oscillation method is also completed. Therheological characteristic test during the process of blood coagulation is achieved byusing the proposed double magnetic circuit magnetic bead oscillatory method. Thesystem has an advanced3D sampling unit, driver embedded point-to-point function,S-curve acceleration and line-circle interpolation motion function, and weak signalsampling-amplifying function. It has the advantages of powerful functions, real-timemultitask operation, rapid detection, and high accuracy.
This thesis lays a good foundation to build the necessary theoretical principle thatwill benefit the research on the biorheological characteristic testing method and itsapplication. It has important directive significance to the development of thebiofluid rheological characteristic testing method.
论文首先全面综述了流变学的国内外研究现状，阐述了非牛顿流体流变学研究领域的分类及研究的重要意义，详细分析了血液流变学、细胞流变学、血液凝固过程中的流变机理和参数测量等生物流变学特性测试的研究内容，阐明了生物流变学与心脑血管疾病、恶性肿瘤及糖尿病等多种疾病的关系以及生物流变学在血液流动状态下对止血、凝血及血栓形成中的生理、病理作用及临床意义。
其次以流变学的研究对象和研究方法为基础，全面阐述了非牛顿流体流变学测量理论，对非牛顿流体流动与变形进行了力学分析，推导出非牛顿流体流动的基本微分方程，构建了纯粘性非牛顿流体的本构方程，分析了非牛顿流体的典型流动以及流体粘弹性与触变性等流变性质，重点研究了稳态剪切流场的主要流变学参数和小振幅振荡流场与流体粘弹性的流变学参数表征方法。
针对生物流变学特性测试研究，提出了稳态剪切速度衰减血流变测试方法、基于激光衍射和散射技术的细胞形态、变形与聚集等细胞流变学特性测试方法以及基于小振幅振荡流场的双磁路磁珠振荡法、光学散射测量法和发色底物测量法的等血液凝固过程中的流变特性测试方法，解决了生物流变学领域的血液流动性、细胞变形性、细胞聚集性以及血液凝固性等一系列生物流体流变学特性测试技术与方法。
提出了基于稳态剪切流场、拉伸流场和小振幅振荡流场的生物流变学特性测试特性模型，建立了高灵敏度、高可靠性的库特式生物流体流变学特性测试系统和动态数据建模平台，采用应力驱动、实时频率扫描、小振幅振荡和强迫振荡四种模式实现生物流体流变学特性测试及动态数据建模。
论文对提出的稳态剪切速度衰减血流变测试方法和激光衍射细胞流变学特性测试方法进行了实验验证，针对目前非牛顿流体流变特性测试仪器无法标定以及测试结果无法溯源等问题，研制了一种稳定可靠的非牛顿流体标准物质，提出了非牛顿流体标定方法。
完成了基于稳态剪切速度衰减测试方法的血流变测试系统应用研究。系统采用提出的速度衰减法锥板测试技术实现全量程、逐点扫描、快速、稳态的血流变特性测量，具有自动加样、自动混匀、自动测试、自动清洗、液面感应等先进功能，具有非牛顿流体标准物质标定和校准功能。
完成了基于双磁路小振幅振荡测试方法的凝血测试系统应用研究。利用提出的双磁路磁珠振荡法测量原理实现血液凝固过程中的流变特性功能测试。系统具有先进的三维空间加样系统、驱动器内置点到点功能、S曲线加速、直线/圆弧插补运动功能以及微弱信号采集放大功能。系统具有功能强大、实时多任务操作、检测速度快、精度高等特点。
本论文的研究为生物流变学特性测试方法及应用奠定了必要的理论基础，对于推动我国生物流变学特性测试技术研究有着重要的指导意义。
Rheology is a science that studies the time-related deformation and flow ofnon-Newtonian fluids under the conditions of stress, strain, and temperature. It is aninterdisciplinary subject which includes some parts of physics, mechanics, medicine,biology, and engineering. The flow of viscoelastic fluids, viscoplastic fluids, bloods,and most of biofluids demonstrates the characteristics of non-Newtonian fluid. Thetesting of some rheological characteristics, such as the rheological characteristics ofnon-Newtonian fluids, mechanical analysis of fluid flow and deformation,constitutive equations of fluids, parameters and functions of material,viscosity-temperature characteristics of fluids, flow curve, coagulability,viscoelasticity, and thixotropy, demands prompt solution. Especially in the field ofbiomedical engineering, the test problems about the biorheological characteristics,such as the dynamics of blood flow, deformation laws of blood cell, mechanicalproperts of blood, other body fluids, and all kinds of soft and hard tissues, andrelations between the rheological characteristics of biofluids and illnesses, are raisedin succession. Hemorheology, cell rheology, and the rheological mechanism andparameter measurement during the process of blood coagulation, have attractedmany researcher’s attention. This thesis focuses on the research on thebiorheological characteristic testing method and its applications, along with theresearch project Rheological Characteristic Testing Methods in Hemorheology, CellRheology, and the Process of Blood Coagulation.
An overall review of the rheology is given. The classification and researchsignificance of the non-Newtonian fluid rheology are introduced. Research topics ofthe biorheological characteristic testing, such as the hemorheology, cell rheology,and the rheological mechanism and parameter measurement during the process ofblood coagulation, are analyzed in detail. The relations between the biorheology andsome illnesses such as cardiovascular and cerebrovascular disease, malignant tumor,and diabetes, are revealed. The physiological and pathological actions of thebiorheology towards the hemostasis, blood coagulation, and formation of thrombuswhile the blood flows are discussed.
Based on the research object and method of rheology, the measurement theory of non-Newtonian fluid rheology is introduced. The mechanical characteristics of thenon-Newtonian fluid deformation and flow are analyzed. Basic differentialequations of the non-Newtonian fluid flow are deduced. Constitutive equations ofthe pure viscous non-Newtonian fluids are built. Some typical flows ofnon-Newtonian fluid, and rheological characteristics such as viscoelasticity andthixotropy, are analyzed. The main rheological parameters of the steady state shearflow field and the rheological parameter characterization methods of the smallamplitude oscillatory flow field and fluid viscoelasticity are studied.
According to the research on the biorheological characteristic testing technique, ahemorheological test method based on steady state shear velocity attenuationmethod is presented. A test method of cell rheological characteristic, such as cellmorpha, deformation and aggregation, based on the technique of laser diffractionand scattering is proposed. Rheological characteristic test methods during theprocess of blood coagulation, such as double magnetic circuits magnetic beadoscillatory method, optical scattering measuring method and chromogenic substratemeasuring method, based on the small-amplitude oscillatory flow field, are alsodemonstrated. The problems of some test techniques and methods of biorheologicalcharacteristic, such as the blood flow, cell deformation, cell aggregation and bloodcoagulation, are resolved.
Biorheological characteristic test models are given based on steady state shearflow field, elongational flow field, and small-amplitude oscillatory flow field. Ahighly sensitive and reliable Couette biofluid rheological characteristic test systemand dynamic data modeling system are built. The biofluid rheological characteristictest and dynamic data modeling are accomplished by using the models of stressdriving, real-time frequency sweep, small amplitude oscillation, and forcedoscillation.
Experiments are conducted to verify the proposed hemorheological test methodbased on steady state shear velocity attenuation method and cell rheological testmethod based on laser diffraction method. To sovle the problems that theinstruments for non-Newtonian fluid rheological characteristic testing cannot becalibrated and its testing results cannot be traced, a kind of stable and reliablenon-Newtonian fluid standard substance is developed and a non-Newtonian fluidcalibration method is proposed.
The application research on hemorheological test system based on steady stateshear velocity attenuation method is completed. The system realizes the full-range,point-by-point scanning, rapid and steady-state measurement of the hemorheologicalcharacteristics using the proposed velocity attenuation cone-plate testing method.The system has some advanced functions such as automatic sampling, blending,testing, and cleaning, together with the function of liquid level detecting. It also hasthe functions of non-Newtonian fluid standard substance calibration and adjustment.
The application research on blood coagulation test system based on doublemagnetic circuit small amplitude oscillation method is also completed. Therheological characteristic test during the process of blood coagulation is achieved byusing the proposed double magnetic circuit magnetic bead oscillatory method. Thesystem has an advanced3D sampling unit, driver embedded point-to-point function,S-curve acceleration and line-circle interpolation motion function, and weak signalsampling-amplifying function. It has the advantages of powerful functions, real-timemultitask operation, rapid detection, and high accuracy.
This thesis lays a good foundation to build the necessary theoretical principle thatwill benefit the research on the biorheological characteristic testing method and itsapplication. It has important directive significance to the development of thebiofluid rheological characteristic testing method.
引文
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