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Modelling and Analysis of Nanoparticles Transport in a Microfluidic Channel for Enhancing the Sensitivity of Immunoassay : 면역진단의 민감도 향상을 위한 미세유로에서의 나노 입자 유동 모델링 및 분석

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dc.contributor.advisor안성훈-
dc.contributor.author최성학-
dc.date.accessioned2020-10-13T02:42:16Z-
dc.date.available2020-10-13T02:42:16Z-
dc.date.issued2020-
dc.identifier.other000000163179-
dc.identifier.urihttps://hdl.handle.net/10371/169174-
dc.identifier.urihttp://dcollection.snu.ac.kr/common/orgView/000000163179ko_KR
dc.description학위논문 (박사) -- 서울대학교 대학원 : 공과대학 기계항공공학부(멀티스케일 기계설계전공), 2020. 8. 안성훈.-
dc.description.abstractThis study analyses the binding characteristics of analytes in a microfluidic channel using nanoparticles in order to provide design parameters and establish a database for biosensor. Sample containing model analytes flowed along the microfluidic channel and the binding characteristics are analyzed experimentally by counting the number of analytes bound to the receptors according to the analyte concentration, sample flow rate, and the dimension of the microfluidic channel. A mathematical model for the transport of analytes is also presented based on a probability density function for Brownian motion. The empirical coefficient for the mathematical model is obtained using the experimental results, which remains valid for all different parameters such as analyte concentration, sample flow rate, and the observation position so that the generality of the model is verified. The results show the number of binding efficiency increases as the flow rate decreases and the observation position is closer to the inlet, but it is consistent with the concentration of the sample. The binding characteristics according to the dimension of the microfluidic channel are investigated with the mathematical model and the critical height is dependent on the observation position.
A simple method for enhancing the sensitivity of immunoassay is also presented by agitating the flow using dummy particles. By adding dummy particles into the sample, the transport of analytes towards receptors is enhanced and the effect of dummy particles increases as the volume fraction or size of dummy particles increases, and the flow rate of sample increases. The improved value is analyzed through numerical simulation which shows valid estimation comparing with the experimental results.
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dc.description.abstract본 연구에서는 바이오센서에 대한 설계지표 확보 및 데이터베이스 구축을 위해 미세유로 내에서 나노입자를 이용하여 검출물의 거동특성 및 결합특성을 분석하였다. 먼저 검출물이 포함된 시료를 미세유로에 흘려준 후 시료의 유속, 검출시간, 시료의 농도, 관측위치에 따른 수용체와 결합된 검출물의 개수를 계수함으로써 실험적인 연구를 수행하였다. 또한 미세유로 내에서 검출물의 거동에 대한 모델을 브라운운동에 의한 확률밀도함수를 기반으로 하여 제시하였다. 이 때, 계수 C는 실험결과를 통하여 얻을 수 있었고, 이는 다른 유속조건이나 관측지점에 대해서도 유효한 예측이 가능한 것을 실험결과와 비교해봄으로써 확인하였다. 그 결과 결합효율은 유속이 감소할수록, 관측위치가 주입구로부터 가까울수록 증가했고 모델의 외삽을 통해 미세유로의 높이에 따른 결합효율을 조사해본 결과 관측위치에 따라 최적높이가 달라지는 결과를 보였다.
또한 면역진단의 민감도 향상을 위한 방법으로 본 연구에서는 마이크로입자를 이용하여 유동에 국소적인 교반을 일으키는 방법을 제시하였다. 마이크로 입자를 시료에 첨가함으로써 검출물의 검출 효율이 증가하였으며 이 효과는 입자의 첨가량 및 크기가 증가함에 따라, 그리고 유속이 증가함에 따라 향상되는 것을 실험적으로 확인하였다. 입자 첨가에 의한 향상분은 수치해석을 이용하여 예측할 수 있었으며 그 결과 실험 결과와 일치하는 것을 확인할 수 있었다.
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dc.description.tableofcontents1. Introduction 1
1.1. Biosensor 1
1.1.1. Biosensing 1
1.1.2. Characteristics of biosensors 2
1.1.3. Classification of biosensors 3
1.1.4. Sensing mechanism for a surface detection system 5
1.2. Sensitivity enhancement for a biosensor 7
1.2.1. Improving surface-to-volume ratio 7
1.2.2. Lateral-directional movement of analyte 10
1.3. Purpose of research 12
1.4. This thesis 14
1.4.1. Suggestion for a transport model of analytes in a microfluidic channel for a biosensor 14
1.4.2. Cost-effective and instrument-independent method to enhance the sensitivity of a biosensor 14
Reference 16

2. Transport and the binding phenomenon of analytes in a microfluidic channel 20
2.1. Overview 20
2.2. Streptavidin-biotin binding 21
2.3. Microfluidic channel and surface modification 21
2.4. Investigation for bound particles 24
2.5. The number of bound particles 27
2.5.1. Concentration effect 28
2.5.2. Flow rate effect 30
2.5.3. Effect of observation position from the inlet 33
2.5.4. Effect of ionic strength and surfactant 33
Reference 33

3. Transport model of analytes in a microfluidic channel for biosensor 40
3.1. Overview 40
3.2. Model description 43
3.2.1. A mathematical model for transport of analyte based on Brownian motion 43
3.2.2. Diffusion coefficient of biotinylated bead 47
3.3. The empirical coefficient for the mathematical model 50
3.4. Numerical estimation for the number of bound particles 54
3.4.1. Comparison of the number of bound particles from experiment and mathematical model 54
3.4.2. Mean relative errors 58
3.4.3. Effect of observation position from inlet and channel height 61
Reference 66

4. Enhancement of sensitivity using dummy particles 67
4.1. Overview 67
4.2. Rotational motion of dummy particles 69
4.2.1. Fabrication of microfluidic channel 69
4.2.2. Dummy particle preparation 70
4.2.3. Observation of rotational motion of dummy particles in PDMS channel 72
4.3. The number of bound particles with dummy particles 74
4.3.1. Experimental methods 74
4.3.2. Effect of dummy particle volume fraction 77
4.3.3. Effect of flow rate and dummy particle size 79
Reference 84

5. Analysis of the dummy particle effect 85
5.1. Overview 85
5.2. Model description 85
5.2.1. Depth of binding zone 85
5.2.2. The number of analytes transported into the binding zone by dummy particles 88
5.3. Numerical simulation 90
5.3.1. Computational domain and boundary conditions for numerical simulation 90
5.3.2. Lateral velocity induced by dummy particles 91
5.3.3. Numerical estimation for the number of bound particles 96
Reference 98
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dc.language.isoeng-
dc.publisher서울대학교 대학원-
dc.subjectBiosensor-
dc.subjectSensitivity of immunoassay-
dc.subjectTransport of analyte-
dc.subjectMicrofluidic channel for biosensor-
dc.subject.ddc621-
dc.titleModelling and Analysis of Nanoparticles Transport in a Microfluidic Channel for Enhancing the Sensitivity of Immunoassay-
dc.title.alternative면역진단의 민감도 향상을 위한 미세유로에서의 나노 입자 유동 모델링 및 분석-
dc.typeThesis-
dc.typeDissertation-
dc.contributor.AlternativeAuthorChoi Sunghak-
dc.contributor.department공과대학 기계항공공학부(멀티스케일 기계설계전공)-
dc.description.degreeDoctor-
dc.date.awarded2020-08-
dc.contributor.major멀티스케일기계설계-
dc.identifier.uciI804:11032-000000163179-
dc.identifier.holdings000000000043▲000000000048▲000000163179▲-
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