MEMS RESONANT MASS SENSING WITH ENABLED OPTICAL INTERACTION FOR CELLULAR STUDY

Abstract

The precision and mass sensitivity of nano- and micro-resonators is unmatched, revealing mechanical properties on progressively diminishing size-scales. Such lofty promises to deliver high resolution in robust and versatile applications require an equally precise method to observe and control nano- and micro-sized particles as they undergo mass and density characterization. This capability has profound implications in the fields of medicine and biology, in characterizing key parameters of the most basic unit of life, the cell. Observation of cell mass/density can answer many fundamental questions in biology and medical disease research, with the potential to investigate direct therapeutic interactions on the single-cell level and target rapid drug feedback. These meaningful results generally describe a distribution of measurements repeated for many cells over long experimental durations, where microfluidics can aid in serial sampling when integrated with resonant mass sensors. However, this fluidic environment is often isolated from observation by the macro-scaled world, which imposes some critical challenges and limitations. Especially for repeated observations of samples with temporally-varying characteristics, sources of measurement error can defeat the resolution of small mass changes, indicative of cellular processes or perturbation effects. One such error source derives from the two-sided response of mass sensitivity in a resonator, involving both the position and mass of the added sample. Spatial fixation or careful observation of sample position can mitigate this effect for better measurement stability and repeatability. To this end, this dissertation investigates optical manipulation (trapping) and observation of particles and cells in fluid as a viable method to achieve better experimental fidelity and extend applications of this approach. Such a capability is not trivial; in fact, it imposes important challenges on both device and system development, and optical trapping itself mandates special design methods for integration with micro-electro-mechanical system (MEMS) mass-sensing platforms. With the introduction of manipulation, optical exposure becomes an especially important consideration when working with biological cells, organic matter, or other materials adversely affected by impinging high intensity laser light. Accordingly, inclusion of an integrated optical substrate (photonic crystal) can bolster high trap efficiency, and in this way, the devices can extend biological viability by reducing optical intensity, an important concern for experiments involving living cells. More global application of these devices also finds them compatible with other essential optical tools, such as fluorescence microscopy or flow cytometry. This work discloses design and fabrication development instrumental in uniting these important technologies, embodied by unique devices with maintained compatibility with MEMS processing. Accordingly, these devices demonstrate suitability for optical trapping, microscopy, and mass sensing, and the effects of optical manipulation on the measurement are disclosed, toward long-term biological mass monitoring and sensing.