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Ultrasensitive Detection of RBC Deformability Using Microfluidic Chips for Assessing Human Aging

미세유체 칩을 이용한 인간 노화 평가를 위한 초고감도 적혈구 변형능 측정

  • Jihee You (유지희, 대학원 기계공학과 기계공학전공)

초록/요약

Red blood cell (RBC) deformability is a critical determinant of microvascular flow and oxygen delivery and holds potential as a biomarker for aging and various pathological conditions. However, current hematological techniques lack the precision to distinguish age-related differences in RBC deformability. To address this limitation, this study aimed to develop an ultrasensitive method to accurately assess the decline in deformability associated with aging. We designed a device incorporating a porous section formed by filling a 400 μm diameter, 2 mm long tube with 20 μm or 25 μm beads. RBCs with greater deformability traversed this porous section more quickly, achieving greater migration distances and higher velocities. Hematocrit levels were carefully standardized to ensure consistency in measurements. RBC deformability was measured in mice aged 1, 6, 12, 18, 24, and 30 months, revealing statistically significant age-related differences. For human RBCs, aggregation posed a challenge, which was mitigated by diluting samples to 60%. To enhance the detection of age-related differences, osmolarity was adjusted to 170 mOsm. Under these conditions, a clear distinction in deformability was observed between the younger group and the older group. Additionally, ROC curve analysis validated the microfluidic chip as a reliable biomarker for aging, achieving an AUC of 0.8393 with 69.57% sensitivity and 82.61% specificity in distinguishing young and old individuals. This study demonstrates that RBC deformability is a valid indicator of age-related changes. In the future, this method could be applied to estimate physiological age, evaluate systemic aging, and assess oxygen delivery efficiency. The findings highlight the potential of this approach in personalized medicine and aging research.

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목차

ABSTRACT i
국문 초록 iii
TABLE OF CONTENTS v
LIST OF TABLES vii
LIST OF FIGURES viii
CHAPTER 1. INTRODUCTION 1
CHAPTER 2. RESEARCH BACKGROUND 5
2.1 RBC as a Biomarker of Human Aging 5
2.2 RBC Deformability 7
2.3 Measurement of RBC Deformability 9
2.4 Microfluidic system 13
CHAPTER 3. MATERIALS AND METHOD 15
3.1 Blood collection 15
3.2 Instrumentation 15
3.3 Microfluidic Chip for RBC deformability 15
3.4 Effect of bead size 19
3.5 PBS diliution & washing of RBC 22
3.6 RBC Deformability according to Osmotic stress 26
3.7 Statistical Analysis 30
CHAPTER 4. RESULTS 32
4.1 Pre-study Cohort description 32
4.2 Pre-clinical study 35
4.3 Study Cohort description 38
4.4 Clinical study 41
CHAPTER 5. DISCUSSION 44
CHAPTER 6. CONCLUSSION 46
REFERENCES 49
ACKNOWLEDGEMENT 55

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