Suspended Microchannel Resonators for Ultralow Volume Universal Detection

Abstract

Universal detectors that maintain high sensitivity as the detection volume is reduced to the sub-nanoliter scale can enhance the utility of miniaturized total analysis systems (ji-TAS). Here the unique scaling properties of the suspended microchannel resonator (SMR) are exploited to show universal detection in a 10 pL analysis volume with a density detection limit of -1 [gg/cm 3 (10 Hz bandwidth) and a linear dynamic range of six decades. Analytes with low UV extinction coefficients such as polyethylene glycol (PEG) 8 KDa, glucose, and glycine are measured with molar detection limits of 0.66 RM, 13.5 gM, and 31.6 JIM, respectively. To demonstrate the potential for real-time monitoring, gel filtration chromatography was used to separate different molecular weights of PEG as the SMR acquired a chromatogram by measuring the eluate density. This work suggests that the SMR could offer a simple and sensitive universal detector for various separation systems from liquid chromatography to capillary electrophoresis. Moreover, since the SMR is itself a microfluidic channel, it can be directly integrated into g-TAS without compromising overall performance. AcknowledgementsFirst of all, I wish to thank Professor Scott Manalis for the opportunity to do my thesis research in his laboratory. Scott has given me invaluable guidance that fosters creativity, teamwork, enthusiasm, and handson research. I also want to thank all group members who contributed to this work: Thomas Burg originally developed the SMR and related setups which I used for my research inline with HPLC system. He also gave me countless advices regarding experiment. Will Grover was an indispensable resource for everything from the knowledge involving HPLC to experimental details. Michel Godin was a good consultant who gave me an insight to research in general. Scott Knudsen helped me dealing with problems involving chemistry and biology with great passion. Yao-Chung (Wesley) Weng gave me a great help in dealing with electronics such as oscillating circuits. Furthermore, the passion of Rumi Chunara, diligence of Andrea Bryan, optimism of Marcio von Muhlen, and discretion of Phillp Dextras has been constant sources of motivation for me. I also thank Ken Babcock and Alison Skelley for valuable discussions.

Nonmonotonic Energy Dissipation in Microfluidic Resonators

“…Such devices enable mass measurements of nanoparticles, single bacterial cells, and submonolayers of adsorbed proteins with femtogram sensitivity in liquid [9]. Applications also include ultralow volume universal detection for liquid chromatography [10], the measurement of fluid density [11][12][13], and the measurement of mass flow [14].A key outstanding question is how energy dissipation, and hence sensitivity, scales with the size of the resonator and the density and viscosity of the fluid. We investigate the effect of the fluid only; variations in the intrinsic quality factor with size have been investigated elsewhere [15].…”

“…Such devices enable mass measurements of nanoparticles, single bacterial cells, and submonolayers of adsorbed proteins with femtogram sensitivity in liquid [9]. Applications also include ultralow volume universal detection for liquid chromatography [10], the measurement of fluid density [11][12][13], and the measurement of mass flow [14].…”

Nanomechanical identification of liquid reagents in a microfluidic channel

“…First, the development of resonating suspended microchannel structures by the groups of Stemme 5 and Manalis, 6 allows ultrasensitive mass measurements for biomolecules, nanoparticles, microbes, and cells in liquid, as well as liquid reagents using mechanical resonance. [6][7][8][9][10] This breakthrough, which places the liquid inside a resonator instead of using the conventional method of placing the resonator in a liquid, overcomes the limitation of damping-induced low sensitivity in the mass-based detection. Although it adds extremely high sensitivity to mass density [11][12][13] and viscosity detection, 14,15 it does not provide chemical selectivity.…”

Beam model and three dimensional numerical simulations on suspended microchannel resonators

“…However, although the response is prompt, such a conventional microcantilever device is usually immersed in the fluid, and hence suffers from the viscous damping and virtual mass from fluid, yielding low quality factor (Q-factor) and degraded resolution. In addition to the traditional micromechanical mass biosensors, a vibrational biosensor of the both-ends-supported microbeam, 10 a fluid-density sensor, 11,12 and a suspended microchannel resonator [13][14][15] have been proposed in the recent decade. It is particularly interesting to mention that for the fluid-density sensor and the suspended microchannel resonator, which are distinct from the usual micromechanical mass biosensor, buffer solutions are transported within the microchannel of the biosensor.…”