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Linda G. Griffith. Inman, Samuel Walker Massachusetts Institute of Technology. Dept. of Mechanical Engineering. Massachusetts Institute of Technology. Department of Mechanical Engineering 2011-12-09T21:28:12Z 2011-12-09T21:28:12Z 2011 2011 http://hdl.handle.net/1721.1/67586 763419468 Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2011. Cataloged from PDF version of thesis. Includes bibliographical references (p. 115-117). In vitro models that capture the complexity of human tissue and organ behaviors in a scalable and easy-to- use format are of increasing interest for both technological applications in drug development and in basic biology research. Tissues and organs are perfused continuously with blood, which delivers nutrients, oxygen, and macromolecular regulatory molecules. In vitro culture models that incorporate local micro-perfusion in a format that allows accesses to cells and their microenvironment are desirable to a broad research community. This thesis describes a platform that features an array of bioreactors that foster three dimensional tissue organization under continuous perfusion. Each bioreactor contains a scaffold that supports formation of hundreds of 3D microscale tissue units. Perfusion through the tissue is achieved using integrated pneumatic diaphragm micropumps. Pumps continuously circulate cell culture medium within each of the fluidically isolated bioreactors in the array. Pulsatile flow from the pumps is filtered using integrated fluidic capacitors such that the flow rate through the scaffold is constant. The format of the device mimics the familiar multiwell tissue culture plate and is easily integrated into existing laboratory facilities. One desirable feature for both parsing metabolic function and assessing response to treatments is a real time read out of oxygen tension at key points in the bioreactor. Such added dimension of real time measurement significantly enhances the value of a cue-response experiment such as a liver drug toxicology study. The thesis describes optical oxygen sensors that measure the florescence decay time of a ruthenium complex, which varies predictably in different oxygen environments. The sensors excite a layer of ruthenium glued to the end of an optical fiber using a stochastic signal from a light emitting diode (LED). The response is then measured on a photodiode. System identification techniques are used to determine the relevant time constants which are subsequently converted to oxygen measurements. Application to real time monitoring of liver tissue function is used for illustration of the utility of the measurements. by Samuel Walker Inman. Ph.D. 125 p. eng Massachusetts Institute of Technology 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 Mechanical Engineering. Integration of real time oxygen measurements with a 3D perfused tissue culture system Thesis application/pdf false Publication unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="14baec12-7ff7-411b-9524-ee54fc47ab15"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Language>eng</Language> <Title>Integration of real time oxygen measurements with a 3D perfused tissue culture system</Title> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2011</PublicationDate> <Authors> <Author> <DisplayName>Inman, Samuel Walker</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>http://dspace.mit.edu/handle/1721.1/7582</License> <Keyword>Mechanical Engineering.</Keyword> <Abstract>In vitro models that capture the complexity of human tissue and organ behaviors in a scalable and easy-to- use format are of increasing interest for both technological applications in drug development and in basic biology research. Tissues and organs are perfused continuously with blood, which delivers nutrients, oxygen, and macromolecular regulatory molecules. In vitro culture models that incorporate local micro-perfusion in a format that allows accesses to cells and their microenvironment are desirable to a broad research community. This thesis describes a platform that features an array of bioreactors that foster three dimensional tissue organization under continuous perfusion. Each bioreactor contains a scaffold that supports formation of hundreds of 3D microscale tissue units. Perfusion through the tissue is achieved using integrated pneumatic diaphragm micropumps. Pumps continuously circulate cell culture medium within each of the fluidically isolated bioreactors in the array. Pulsatile flow from the pumps is filtered using integrated fluidic capacitors such that the flow rate through the scaffold is constant. The format of the device mimics the familiar multiwell tissue culture plate and is easily integrated into existing laboratory facilities. One desirable feature for both parsing metabolic function and assessing response to treatments is a real time read out of oxygen tension at key points in the bioreactor. Such added dimension of real time measurement significantly enhances the value of a cue-response experiment such as a liver drug toxicology study. The thesis describes optical oxygen sensors that measure the florescence decay time of a ruthenium complex, which varies predictably in different oxygen environments. The sensors excite a layer of ruthenium glued to the end of an optical fiber using a stochastic signal from a light emitting diode (LED). The response is then measured on a photodiode. System identification techniques are used to determine the relevant time constants which are subsequently converted to oxygen measurements. Application to real time monitoring of liver tissue function is used for illustration of the utility of the measurements.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>