Suspended microchannel resonators for biomolecular detection

Abstract

Microfabricated transducers enable the label-free detection of biological molecules in nanoliter sized samples. Integrating microfluidic detection and sample-preparation can greatly leverage experimental efforts in systems biology and pharmaceutical research by increasing analysis throughput while dramatically reducing reagent cost. Microfabricated resonant mass sensors are among the most sensitive devices for chemical detection, but degradation of the sensitivity in liquid has so far hindered their successful application in biology. This thesis introduces a type of resonant transducer that overcomes this limitation by a new device design: Adsorption of molecules to the inside walls of a suspended microfluidic channel is detected by measuring the change in mechanical resonance frequency of the channel. In contrast to resonant mass sensors submersed in water, the sensitivity and frequency resolution of the suspended microchannel resonator is not degraded by the presence of the fluid. Our device differs from a vibrating tube densitometer in that the channel is very thin, and only molecules that bind to the walls can build up enough mass to be detected; this provides a path to specificity via molecular recognition by immobilized receptors.

(cont.) Suspended silicon nitride channels have been fabricated through a sacrificial polysilicon process and bulk micromachining, and the packaging and microfluidic interfacing of the resonant sensors has been addressed. Device characterization at 30 mTorr ambient pressure reveals a quality factor of more than 10,000 for water filled resonators; this is two orders of magnitude higher than previously demonstrated Q-values of resonant mass sensors for biological measurements. Calculation of the noise and the sensitivity of suspended microchannel resonators indicate a physical limit for mass resolution of approximately 0.01 ng/cm2 (1 Hz bandwidth). A resolution of -0.1 ng/cm2 has been experimentally demonstrated in this work. This resolution constitutes a tenfold improvement over commercial quartz crystal microbalance based instruments. The ability to detect adsorbing biomolecules by resonance frequency has been validated through binding experiments with avidin and various biotinylated proteins.