Suspended microchannel resonators for biomolecular detection

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2005. === Includes bibliographical references (leaves 115-124). === Microfabricated transducers enable the label-free detection of biological molecules in nanoliter sized samples. Integratin...

Full description

Bibliographic Details
Main Author: Burg, Thomas P. (Thomas Peter)
Other Authors: Scott R. Manalis.
Format: Others
Language:English
Published: Massachusetts Institute of Technology 2006
Subjects:
Online Access:http://hdl.handle.net/1721.1/34471
id ndltd-MIT-oai-dspace.mit.edu-1721.1-34471
record_format oai_dc
spelling ndltd-MIT-oai-dspace.mit.edu-1721.1-344712019-05-02T15:39:46Z Suspended microchannel resonators for biomolecular detection Burg, Thomas P. (Thomas Peter) Scott R. Manalis. Massachusetts Institute of Technology. Dept. of Electrical Engineering and Computer Science. Massachusetts Institute of Technology. Dept. of Electrical Engineering and Computer Science. Electrical Engineering and Computer Science. Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2005. Includes bibliographical references (leaves 115-124). 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. by Thomas P. Burg. Ph.D. 2006-11-07T12:25:21Z 2006-11-07T12:25:21Z 2005 2005 Thesis http://hdl.handle.net/1721.1/34471 70720170 eng M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 124 leaves 22158996 bytes 22158782 bytes application/pdf application/pdf application/pdf Massachusetts Institute of Technology
collection NDLTD
language English
format Others
sources NDLTD
topic Electrical Engineering and Computer Science.
spellingShingle Electrical Engineering and Computer Science.
Burg, Thomas P. (Thomas Peter)
Suspended microchannel resonators for biomolecular detection
description Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2005. === Includes bibliographical references (leaves 115-124). === 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. === by Thomas P. Burg. === Ph.D.
author2 Scott R. Manalis.
author_facet Scott R. Manalis.
Burg, Thomas P. (Thomas Peter)
author Burg, Thomas P. (Thomas Peter)
author_sort Burg, Thomas P. (Thomas Peter)
title Suspended microchannel resonators for biomolecular detection
title_short Suspended microchannel resonators for biomolecular detection
title_full Suspended microchannel resonators for biomolecular detection
title_fullStr Suspended microchannel resonators for biomolecular detection
title_full_unstemmed Suspended microchannel resonators for biomolecular detection
title_sort suspended microchannel resonators for biomolecular detection
publisher Massachusetts Institute of Technology
publishDate 2006
url http://hdl.handle.net/1721.1/34471
work_keys_str_mv AT burgthomaspthomaspeter suspendedmicrochannelresonatorsforbiomoleculardetection
_version_ 1719026050475753472