On-chip biosensing using magnetic particles

Abstract

In the recent years, there is a growing interest in microfluidic platforms using magnetic particles in combination with magnetic sensors seeking to tackle a wide range of challenges in biomedicine and biotechnology. The goal of this thesis is to propose such platforms utilizing unexplored methods for pathogen detection, biomolecule resolution, biomolecule quantification and rare cell trapping for further analysis. The first part of this work (Chapters 2 - 4) presents a biosensor for bacteria detection using the magnetically induced motion of functionalized superparamagnetic microparticles (SMPs). The concept of the proposed method is that the induced velocity on SMPs in suspension, while imposed to a magnetic field gradient, is inversely proportional to their volume. Specifically, a velocity variation of the functionalized SMPs inside a detection microchannel with respect to a reference velocity, specified in a parallel reference microchannel, indicates an increase in their non-magnetic volume. This volumetric increase of the SMPs is caused by the binding of organic compounds (e.g. bacteria) on their functionalized surface. During the course of the experiments for the aforementioned biosensor, it was realized that friction plays an important role in the motion of particles that were in contact with the chip-s surface. Out of that observation, a biosensor for the detection of biomolecules is proposed, where the friction is for the first time utilized for the resolution of biomolecules. The principle is used for the development of an antibody detection system. The results were verified with Atomic Force Microscopy (AFM) measurements (Chapter 5). Furthermore, a modified biosensor system is used for the detection and quantification of nanomarkers due to their high biomedical relevance. Firstly, detection of commercial Nanomag-D particles of 250 nm diameter is presented (Chapter 6). The results show that the sensor is capable of detecting concentrations as low as 500 pg/-l of Nanomag-D particles and quantifying them in a linear scale over a wide particle concentration range (1 - 500 ng/-l). Subsequently, custom made alginate functionalized nanoparticles are tested and their detection for concentrations of 100 - 1000 ng/-l, over a linear scale is presented (Chapter 7). Lastly, it is reported in both cases, that the particle concentration is correlated to the time the particles need to accumulate on the sensor-s surface. The last part of this work suggests rare cell isolation systems. The first system incorporates a polymer microtrap with integrated current carrying microconductors (Chapter 8). The later drive leukaemia cells tagged with magnetic microparticles towards the microtrap. This entrapment allows for the further analysis of the cells with many advantages in the area of diagnostics and therapeutics. Finally a second isolation cell system is presented (Chapter 9). This time sequentially actuated conductors and giant magnetoresistance sensors are used for trapping and detecting magnetic micromarkers. All the systems presented in this thesis are compact, portable and cost effective lab-on-chip systems. The utilized technologies render them appealing for economies of scale, while their low cost in addition to their straightforward operation make them ideal for Point of Care testing and for laboratories operating in poor conditions.