Microfluidics and Bio-MEMS for Next Generation Healthcare

Abstract

Microfluidics and bio-MEMS technology provide essential tools for next-generation healthcare, in areas such as tissue engineering, disease diagnostics, and embryology. Tissue engineering requires precise in vitro patterning and multilayer assembly of cells and biomaterial scaffolds, and often requires mesoscale structures to be assembled with microscale resolution. A potential method of micromanipulation for in vitro tissue constructs is microassembly by a system employing untethered microrobots. Many microrobots should operate in parallel to increase the throughput of such a bio-micromanipulation system. However, current microrobot systems lack the independent actuation of many entities in parallel. In this dissertation, opto-thermocapillary flow-addressed bubble (OFB) microrobots are studied, and the independent actuation of fifty OFB microrobots in parallel is demonstrated. In addition, individual microrobots and groups of microrobots were moved along linear, circular, and arbitrary 2D trajectories. The independent addressing of many microrobots enables higher-throughput microassembly of micro-objects, and cooperative manipulation using multiple microrobots. Demonstrations of manipulation with numerous OFB microrobots include the transportation of microstructures using a pair or team of microrobots, and the cooperative manipulation of multiple micro-objects. The OFB microrobot system presented here represents an order of magnitude increase in the number of independently actuated microrobots in parallel, as compared to other magnetically or electrostatically actuated microrobots, and a factor of five increase as compared to previous demonstrations of OFB microrobots. Microfluidics provides precise positioning and manipulation of fluids contained in microscale structures. Microfluidic techniques were used to precisely position room-temperature liquid metal in microtubes, enabling tunable capacitors for the receive coil of a magnetic resonance imaging (MRI) scanner. This liquid-metal-based flexible tunable capacitor functions as the tuning element of the MRI receive coil. In this dissertation, four types of liquid-metal-based tunable capacitors with a high tuning range are demonstrated. The capacitors are easily fabricated by placing a pair of liquid-metal-filled tubes in contact with one another. Tunability is achieved by varying the length of the liquid metal in one of the tubes using a mechanical pump. Four different structures are demonstrated: parallel-tube, folded-tube, coil, and spiral capacitors. The highest measured tuning ratio is 42:1, and the highest change in capacitance per unit length of the pumped liquid metal is 0.07 pF.mm-1. Microfabricated sensors and actuators for biomedical applications are known as biomicroelectromechanical systems, or bio-MEMS. In this dissertation, a microfluidic bio-MEMS device was designed and made to study embryo viability, which is critical for successful in vitro fertilization (IVF) treatment. Conventional methods of embryo evaluation rely mostly on subjective visual analysis of embryo morphological features. Here, two different approaches have been studied for automating the morphological embryo grading and developing a quantitative embryo evaluation process free from human subjective errors. In the first approach, the human blastocyst microscope images were analyzed using image processing tools. Their growth dynamics were studied leading to crucial viability information. In the second approach, the embryo was positioned in between two electrodes inside a microfluidic bio-MEMS device, and their electrical impedance was measured during their development. Experiments with Artemia cysts showed a distinct pattern of impedance changes at three different stages of cyst development. The measured impedance changes corresponded to physiological changes as the cyst developed. The change in impedance during the first stage of development provided sufficient quantitative data to predict if the cyst would hatch. This work shows the potential of impedance spectroscopy for developing a non-invasive test to quantitatively determine the health of the embryos.