Emerging biomarker sensors for personalized medicine [electronic resource]

In this dissertation, three technological challenges pertaining to the field of personalized medicine are addressed. These challenges include development of high throughput and multiplexed proteomics technologies, reducing the diagnostic cost per test, and automation and integration of biological sample preparation prior to sensing. Accordingly, a multiplexed platform for protein analysis is developed, a low cost cytometer using contactless impedance sensing is presented, and a two-component microfluidic platform for depletion of cells and unwanted highly abundant proteins from the input sample is demonstrated. To facilitate a multiplexed platform for protein analysis, along a single microfluidic channel, an array of proteins is patterned, where each element is targeting a specific secondary protein coated on micron-sized beads in the subsequently introduced sample solution. Below each element of the array, there is a pair of addressable interdigitated electrodes. By selectively applying voltage at the terminals of each interdigitated electrode pair, the produced negative dielectrophoresis (nDEP) force detaches protein-bound beads from each element of the array, one by one, without disturbing the bound beads in the neighboring regions. The detached beads can be quantified optically or electrically downstream. Here, to allow for robust actuation of micron-sized beads, the relatively weak DEP force was enhanced by two orders of magnitude (beyond the strength of protein-protein interactions) by fabricating high voltage tolerant corrosion proof electrodes. This was achieved by depositing a protective pinhole free nanometer-scale thin film layer on electrodes, using Atomic Layer Deposition technique. In parallel, a comprehensive design space was developed to analyze this enhanced DEP system from both a circuit analysis and electrothermal viewpoints. In our developed model, various phenomena and constraints such as voltage degradation (due to the presence of the protecting oxide layer), oxide breakdown, instrumentation limitations, and thermal effects have been taken into account. The results from this analysis were used to maximize the DEP force in our system. For proof of concept, 16-plex actuation capability of the device is illustrated to elute micron-sized beads that are bound to the surface through anti-IgG and IgG interaction which is on the same order of magnitude in strength as typical antibody--antigen interactions. Next, a novel contactless impedance sensing scheme to perform low-cost cytometry in whole blood is demonstrated. In particular, a disposable microfluidic impedance cytometer is developed using electrodes that can be reused, without the need for microfabrication of the electrodes. This disposable device can be inserted onto a printed circuit board (PCB) which has a non-disposable, yet inexpensive, electronic reading apparatus. This significantly reduces the manufacturing costs, making it suitable for low resource settings, such as point-of-care testing in the developing countries. In the third platform, a microfluidic system that can deplete cells with 100% efficiency and abundant serum proteins from blood with 95% efficiency is presented. The platform consists of two components. The first component is a microfluidic mixer, which mixes beads containing antibodies against the highly abundant proteins with the whole blood. This complex mixture (consisting of beads, cells, and serum proteins) is then injected into the second component of our microfluidic platform, which comprises a filter trench to capture all the cells and the beads. The size-based trapping of the cells and beads into the filter trench is significantly enhanced by leveraging the enhanced DEP force to push the micron sized particles (cells and beads which have captured the highly abundant proteins) down into the trench, allowing the serum proteins of lower abundance to flow through.

Keywords: Electrical Engineering.
Advisor: Dutton Robert W. primary advisor. Thesis advisor
Davis Ronald W. (Ronald Wayne)
Howe Roger Thomas advisor. Thesis advisor
Javanmard Mehdi