Micromachined electromechanical devices for analysis and characterization of a biological entity on a single cell level

With the advent of the MEMS technology, various new possibilities have arisen in the analysis of biological entities. One of the new possibilities is the ability to analyze the heterogeneity of the target entities due to the ability to do measurements at the level of single entities. Typically, the target entities are usually processed and analyzed in large number especially in the field of microbiology, ignoring the heterogeneity of the sample population. MEMS technology can provide versatile tools for manipulating, processing and analyzing a few or single particles, enabling detailed analysis on the physiology and the metabolism of individual entities. The new approach based on MEMS technology can lead us into numerous valuable findings on the physiology and the metabolism of the target entities. In this work, various techniques and devices aimed for a few or single cell analysis of the biological entities were developed, which could be potentially integrated in a single Lab on Chip (LOC) system. A dielectrophoresis (DEP)-based capture and reagentless electrical lysis was implemented on a nano-probe array, which could capture a small number of particles in a fluid with DEP induced by a nano-scale sharp probe and then lyse the particles with a strong electric field generated by the same probe. The DEP-based capture and the electrical lysis of vaccinia virus were demonstrated. For extending the principle of DEP particle manipulation into a real application, a DEP particle manipulation apparatus was developed based on a custom-made printed circuit board without any cleanroom processes. This apparatus can provide a low cost mass-producible platform to implement a DEP particle manipulation in a lab-on-chip system. Finally, and most importantly, for the analysis of a single live cell in fluid, a MEMS-based resonant mass sensor was developed. In one version of this device, the cells were captured in fluid with DEP on a cantilever array and the resonant frequency shift of a cantilever with a single cell was measured to calculate the mass of the cell attached to each cantilever. In a second and significantly improved version of this device, a novel resonant mass sensor with a uniform mass sensitivity was designed and fabricated to overcome the non-uniformity of mass sensitivity of traditional rectangular shaped cantilever-based resonant mass sensors. A new resonant frequency measurement technique with electromagnetic actuation was developed for more precision mass measurement and the mass of HeLa cells was measured using these mass sensors