ME PhD Dissertation Defense: Rebecca Taylor (Thursday, Nov 8th at 8:00am)

Rebecca Taylor rebeccat at stanford.edu
Wed Oct 31 15:10:47 PDT 2012


University PhD Dissertation Defense

*Microfabricated tools for functional assessment of developing
cardiomyocytes*

*Rebecca Taylor*
*Advisors: Prof. Beth L. Pruitt and Prof. Ellen Kuhl*


Department of Mechanical Engineering, Mechanics and Computation Division,
Stanford University


*Thursday, November 8th, 2012 at 8:00am (Refreshments at 7:45am)*
*Location:  Mitchell Earth Sciences Building, Hartley Conference Room 130*
http://campus-map.stanford.edu/?id=04-560&lat=37.4264170549&lng=-122.172654692&zoom=17&srch=Mitchell
(Ruth Wattis)


Abstract:

      Ischemic damage following myocardial infarction often leads to heart
failure, contributing to cardiovascular disease’s status as the number one
killer in developed countries. This year an estimated 785,000 people in the
United States alone will have their first heart attack. This underscores
the critical need for cardiac therapies to actively repair damaged tissue.
These therapies will be predicated upon knowledge of the mechanisms of
cardiac growth and disease, including the development of contractile
function and electrophysiological properties in maturing heart cells.

      Two major barriers to this work involve the lack of tools for direct
functional assessment for developing cardiomyocytes: (1) Axial force
generation can not be assessed using current platforms and imaging
techniques. (2) While cardiomyocyte phenotype and twitch power are improved
when these cells are cultured on soft, tissue-like substrates in the 10-15
kPa range, standard* in vitro*microelectrode arrays can not be used to
study electrophysiology with cells cultured on soft, stretchable
substrates. To address these issues, two different classes of device were
microfabricated to perform direct functional assessment of developing
cardiomyocytes.

      A sacrificial layer technique was developed to suspend immature
cardiomyocytes across pairs of widely-separated elastomer microposts.  By
prescribing a physiological cell shape and two-point loading, purely axial
measurements of force generation were made during cardiomyocyte
contraction.  This force post technique achieved unmatched accuracy and
precision, because microposts were directly calibrated using piezoresistive
cantilevers of known stiffness, and in this measurement uncertainty was
shown to be less than biological variation, a critical achievement for an
elastomer technique.  Forces of up to 146 nanoNewtons were measured.  These
forces were much smaller than the microNewton-scale forces reported from
adult cardiomyocytes, suggesting that force generation capacity may
increase with cardiomyocyte development.  This technique provides a window
into the development biology of healthy cardiomyocytes and a means to study
the cardiac disease progression that was previously impossible.

      In addition, to address the need for electrophysiological
characterization of cardiomyocytes grown on soft, stretchable substrates,
two different approaches were used to fabricate stretchable microelectrode
arrays (SMEAs). A microfluidic platform filled with conductive ink and a
flex circuit-based SMEA with a novel geometry were created.  Both SMEAs
maintain planarity and electrical properties throughout cyclic strains of
up to 15%, and enable electrophysiological study of heart cells grown in
biomimetic, soft and stretching environments.

      Microfabrication has been used to develop devices for directly
assessing cardiomyocyte function.  These platforms overcome critical
challenges to the handling, manipulation, and culture of immature
cardiomyocytes, and are relevant for translational research as well as
basic developmental and physiological investigations of stem cell-derived
cardiomyocytes.


Rebecca Taylor

Bio-X and DARE Fellow
Graduate Research Assistant
Microsystems & Biomechanical Computation Groups
Mechanical Engineering
Stanford University
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