MICROFLUIDIC DEVICES FOR ON-LINE MONITORING OF CLINICALLY RELEVANT PROTEINS DURING CARDIOPULMONARY BYPASS PROCEDURES

Open Access
Author:
Yang, Sung
Graduate Program:
Bioengineering
Degree:
Doctor of Philosophy
Document Type:
Dissertation
Date of Defense:
June 19, 2006
Committee Members:
  • Jeffrey D Zahn, Committee Chair
  • Akif Undar, Committee Member
  • Herbert Herling Lipowsky, Committee Member
  • Keefe B Manning, Committee Member
  • Srinivas A Tadigadapa, Committee Member
Keywords:
  • Microfluidic devices
  • blood separation
  • Continuous real time biosensing
  • CPB
Abstract:
It is well known that cardiac surgery induces systemic inflammatory responses, particularly when cardiopulmonary bypass procedures are used. Thus, it is crucial to develop a system which can measure inflammatory responses in a continuous, real time fashion because it will allow physicians or clinicians to understand the relationship between systemic inflammatory responses and cardiopulmonary bypass procedures. The goal of this study was to produce core technologies for the development of a microanalytical system, which can separate blood plasma from whole blood and measure inflammatory responses in a continuous fashion. Throughout this dissertation, two independent microfluidic devices are discussed. In the development of a microfluidic device for continuous, real time blood plasma separation, the Zweifach-Fung effect was utilized to obtain successful blood plasma separation. It was found that a 100 % particle recovery or fluid separation efficiency can be achieved when the flow rate ratio between two daughter channels is maintained higher than a 6 to 1 ratio. By applying a series of design technologies, the microfluidic device was successfully developed and experimentally demonstrated in both bench top and clinical experimental conditions. The device can separate 15 % to 25 % plasma from whole blood depending of hematocrit levels at the device inlet. The plasma selectivity was almost 100 % regardless of the hematocrit level at the device inlet. In order to develop a microfluidic device for continuous biosensing, a novel particle handling concept named ¡°particle cross over¡± was proposed to manipulate micron-sized cytometric beads within microfluidic channels. The continuous biosensing ability was demonstrated by measuring the fluorescent intensity of the bead at the detection window of the device. It was found that the measured fluorescence intensity of the beads is proportional to the concentration of the analyte solution in the range from 50 ng/ml to 200 ng/ml. The detection limit of the device was found to be around 50 ng/ml of biotinylated Fluorescein IsoThioCyanate concentration. Therefore, one can conclude that a microanalytical system for on-line monitoring of clinically relevant proteins can be developed by integrating the two independent microfluidic devices developed in this research.