Beth L. Pruitt
Associate Professor of Mechanical Engineering and, by courtesy, of Molecular and Cellular Physiology
Bio
The Stanford Microsystems Lab works on custom measurements and analysis systems for small scale metrologies including scanning probe microscopy, biomechanics and mechanotransduction assays. We study the mechanics and biology of the sense of touch in C. elegans, the mechanisms and forces of cell adhesion, and the development and response of stem cells and cardiac myocytes to mechanical loading. We design and fabricate most of our own tools and sensors and are interested in the reliable manufacture and operation of micromachined sensors and actuators in harsh environments, measuring nanoscale mechanical behavior, and the analysis, design, and control of integrated electro-mechanical systems. We leverage new tools and answer novel questions in our lab in the areas of physiology, biology, stem cells, neuroscience and cardiology with an eye toward quantitative and fundamental biophysics.
Academic Appointments
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Associate Professor, Mechanical Engineering
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Associate Professor (By courtesy), Molecular & Cellular Physiology
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Member, Bio-X
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Member, Cardiovascular Institute
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Member, Child Health Research Institute
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Faculty Fellow, Stanford ChEM-H
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Member, Stanford Neurosciences Institute
Honors & Awards
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Fellow, ASME (2015)
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Best Poster Awards (2), 2014 ASME NEMB Meeting (2014)
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Stanford Faculty Scholars, Stanford University (2013-2014)
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Best Poster, MEMS in Medicine and Biology meeting (2013)
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Best Abstract Postdoc Research, GRC on Biointerfaces (2012)
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Silas H. Palmer Faculty Scholar in Mechanical Engineering, Stanford University (2010-2014)
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Stanford Clayman Fellow, Stanford University (2010-2011)
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Denice Denton Emerging Leader Award, Anita Borg Institute (2010)
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Best Abstract Award, MEMS in Medicine and Biology meeting (2009)
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Young Faculty Award, DARPA (2009)
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Best Poster, ASME IMECE meeting (2005)
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CAREER Award, NSF (2005)
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Fellowship, Hertz Foundation (1997-2002)
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Future Professors of Manufacturing Fellowship, Stanford University (1997-2002)
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Navy Commendation Medal for teaching and performance excellence, U.S. Naval Academy (1997)
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Integrated Manufacturing Association Fellowship, Stanford University (1991)
Professional Education
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PhD, Stanford, Mechanical Engineering (2002)
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M.Sc, Stanford University, Manufacturing Systems (1992)
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BS, MIT, Mechanical Engineering (1991)
Current Research and Scholarly Interests
The Pruitt microsystems lab works on custom measurements and analysis systems for small scale metrologies including scanning probe microscopy, biomechanics and mechanotransduction assays. We study the mechanics and biology of the sense of touch in C. elegans, the mechanisms and forces of cell adhesion, and the development and response of stem cells and cardiac myocytes to mechanical loading. We design and fabricate most of our own tools and sensors and are interested in the reliable manufacture and operation of micromachined sensors and actuators in harsh environments, measuring nanoscale mechanical behavior, and the analysis, design, and control of integrated electro-mechanical systems. We leverage new tools and answer novel questions in our lab in the areas of physiology, biology, stem cells, neuroscience and cardiology with an eye toward quantitative and fundamental biophysics.
2015-16 Courses
- Brazil Technology and Engineering
OSPGEN 137 (Sum) - Brazil Technology and Engineering
OSPGEN 37 (Sum) - How Stuff Is Made
ME 14N (Aut) - Introduction to Sensors
ME 220 (Spr) - Mechanobiology and Biofabrication Methods
BIOPHYS 342A, ME 342A (Win, Sum) -
Independent Studies (10)
- Directed Investigation
BIOE 392 (Aut, Win, Spr, Sum) - Directed Reading in Biophysics
BIOPHYS 399 (Aut, Win, Spr, Sum) - Engineering Problems
ME 391 (Aut, Win, Spr, Sum) - Engineering Problems and Experimental Investigation
ME 191 (Aut, Win, Spr, Sum) - Experimental Investigation of Engineering Problems
ME 392 (Aut, Win, Spr, Sum) - Graduate Research
BIOPHYS 300 (Aut, Win, Spr, Sum) - Honors Research
ME 191H (Aut, Win, Spr, Sum) - Ph.D. Teaching Experience
ME 491 (Aut, Win, Spr, Sum) - Practical Training
ME 299A (Aut, Win, Spr, Sum) - Practical Training
ME 299B (Aut, Win, Spr, Sum)
- Directed Investigation
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Prior Year Courses
2014-15 Courses
- Brazil Technology and Engineering
OSPGEN 137 (Sum) - Brazil Technology and Engineering
OSPGEN 37 (Sum) - How Stuff Is Made
ME 14N (Aut) - MEMS Laboratory II
ENGR 342 (Win) - Mechanobiology and Biofabrication Methods
ME 342A (Sum) - Micro/Nano Systems Design and Fabrication
ENGR 341 (Aut)
2013-14 Courses
- How Stuff Is Made
ME 14N (Aut) - MEMS Laboratory II
ENGR 342 (Aut)
2012-13 Courses
- How Stuff Is Made
ME 14N (Win) - MEMS Fabrication/Projects
ME 342D (Sum) - Micro/Nano Systems Design and Fabrication
ENGR 341 (Spr)
- Brazil Technology and Engineering
Stanford Advisees
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Postdoctoral Faculty Sponsor
Alexandre Jose Soares Dos Santos Ribeiro -
Doctoral Dissertation Reader (AC)
Blair Benham-Pyle -
Doctoral Dissertation Advisor (AC)
Aleksandra Denisin
Graduate and Fellowship Programs
All Publications
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Multifunctional Integrated Sensors for Multiparameter Monitoring Applications
JOURNAL OF MICROELECTROMECHANICAL SYSTEMS
2015; 24 (4): 810-821
View details for DOI 10.1109/JMEMS.2014.2349894
View details for Web of Science ID 000358952600007
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Self-sensing cantilevers with integrated conductive coaxial tips for high-resolution electrical scanning probe metrology
JOURNAL OF APPLIED PHYSICS
2015; 118 (3)
View details for DOI 10.1063/1.4923231
View details for Web of Science ID 000358429200024
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Spatial distribution of cell-cell and cell-ECM adhesions regulates force balance while maintaining E-cadherin molecular tension in cell pairs
MOLECULAR BIOLOGY OF THE CELL
2015; 26 (13): 2456-2465
Abstract
Mechanical linkage between cell-cell and cell-extracellular matrix (ECM) adhesions regulates cell shape changes during embryonic development and tissue homoeostasis. We examined how the force balance between cell-cell and cell-ECM adhesions changes with cell spread area and aspect ratio in pairs of MDCK cells. We used ECM micropatterning to drive different cytoskeleton strain energy states and cell-generated traction forces and used a Förster resonance energy transfer tension biosensor to ask whether changes in forces across cell-cell junctions correlated with E-cadherin molecular tension. We found that continuous peripheral ECM adhesions resulted in increased cell-cell and cell-ECM forces with increasing spread area. In contrast, confining ECM adhesions to the distal ends of cell-cell pairs resulted in shorter junction lengths and constant cell-cell forces. Of interest, each cell within a cell pair generated higher strain energies than isolated single cells of the same spread area. Surprisingly, E-cadherin molecular tension remained constant regardless of changes in cell-cell forces and was evenly distributed along cell-cell junctions independent of cell spread area and total traction forces. Taken together, our results showed that cell pairs maintained constant E-cadherin molecular tension and regulated total forces relative to cell spread area and shape but independently of total focal adhesion area.
View details for DOI 10.1091/mbc.E14-12-1618
View details for Web of Science ID 000357053400006
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Mechanical strain induces E-cadherin-dependent Yap1 and beta-catenin activation to drive cell cycle entry
SCIENCE
2015; 348 (6238): 1024-1027
View details for DOI 10.1126/science.aaa4559
View details for Web of Science ID 000355276600046
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Cell adhesion. Mechanical strain induces E-cadherin-dependent Yap1 and ß-catenin activation to drive cell cycle entry.
Science
2015; 348 (6238): 1024-1027
Abstract
Mechanical strain regulates the development, organization, and function of multicellular tissues, but mechanisms linking mechanical strain and cell-cell junction proteins to cellular responses are poorly understood. Here, we showed that mechanical strain applied to quiescent epithelial cells induced rapid cell cycle reentry, mediated by independent nuclear accumulation and transcriptional activity of first Yap1 and then β-catenin. Inhibition of Yap1- and β-catenin-mediated transcription blocked cell cycle reentry and progression through G1 into S phase, respectively. Maintenance of quiescence, Yap1 nuclear exclusion, and β-catenin transcriptional responses to mechanical strain required E-cadherin extracellular engagement. Thus, activation of Yap1 and β-catenin may represent a master regulator of mechanical strain-induced cell proliferation, and cadherins provide signaling centers required for cellular responses to externally applied force.
View details for DOI 10.1126/science.aaa4559
View details for PubMedID 26023140
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Mechano-Transduction: From Molecules to Tissues
PLOS BIOLOGY
2014; 12 (11)
View details for DOI 10.1371/journal.pbio.1001996
View details for Web of Science ID 000345627300009
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Mechano-transduction: from molecules to tissues.
PLoS biology
2014; 12 (11)
Abstract
External forces play complex roles in cell organization, fate, and homeostasis. Changes in these forces, or how cells respond to them, can result in abnormal embryonic development and diseases in adults. How cells sense and respond to these mechanical stimuli requires an understanding of the biophysical principles that underlie changes in protein conformation and result in alterations in the organization and function of cells and tissues. Here, we discuss mechano-transduction as it applies to protein conformation, cellular organization, and multi-cell (tissue) function.
View details for DOI 10.1371/journal.pbio.1001996
View details for PubMedID 25405923
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Stable, Covalent Attachment of Laminin to Microposts Improves the Contractility of Mouse Neonatal Cardiomyocytes
ACS APPLIED MATERIALS & INTERFACES
2014; 6 (17): 15516-15526
View details for Web of Science ID 000341544200092
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Stable, covalent attachment of laminin to microposts improves the contractility of mouse neonatal cardiomyocytes.
ACS applied materials & interfaces
2014; 6 (17): 15516-15526
Abstract
The mechanical output of contracting cardiomyocytes, the muscle cells of the heart, relates to healthy and disease states of the heart. Culturing cardiomyocytes on arrays of elastomeric microposts can enable inexpensive and high-throughput studies of heart disease at the single-cell level. However, cardiomyocytes weakly adhere to these microposts, which limits the possibility of using biomechanical assays of single cardiomyocytes to study heart disease. We hypothesized that a stable covalent attachment of laminin to the surface of microposts improves cardiomyocyte contractility. We cultured cells on polydimethylsiloxane microposts with laminin covalently bonded with the organosilanes 3-glycidoxypropyltrimethoxysilane and 3-aminopropyltriethoxysilane with glutaraldehyde. We measured displacement of microposts induced by the contractility of mouse neonatal cardiomyocytes, which attach better than mature cardiomyocytes to substrates. We observed time-dependent changes in contractile parameters such as micropost deformation, contractility rates, contraction and relaxation speeds, and the times of contractions. These parameters were affected by the density of laminin on microposts and by the stability of laminin binding to micropost surfaces. Organosilane-mediated binding resulted in higher laminin surface density and laminin binding stability. 3-glycidoxypropyltrimethoxysilane provided the highest laminin density but did not provide stable protein binding with time. Higher surface protein binding stability and strength were observed with 3-aminopropyltriethoxysilane with glutaraldehyde. In cultured cardiomyocytes, contractility rate, contraction speeds, and contraction time increased with higher laminin stability. Given these variations in contractile function, we conclude that binding of laminin to microposts via 3-aminopropyltriethoxysilane with glutaraldehyde improves contractility observed by an increase in beating rate and contraction speed as it occurs during the postnatal maturation of cardiomyocytes. This approach is promising for future studies to mimic in vivo tissue environments.
View details for DOI 10.1021/am5042324
View details for PubMedID 25133578
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Shielded piezoresistive cantilever probes for nanoscale topography and electrical imaging
JOURNAL OF MICROMECHANICS AND MICROENGINEERING
2014; 24 (4)
View details for DOI 10.1088/0960-1317/24/4/045026
View details for Web of Science ID 000334306100025
- Multifunctional integrated sensor in a 2x2 mm epitaxial sealed chip operating in a wireless sensor node 2014
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Planar patterned stretchable electrode arrays based on flexible printed circuits
JOURNAL OF MICROMECHANICS AND MICROENGINEERING
2013; 23 (10)
View details for DOI 10.1088/0960-1317/23/10/105004
View details for Web of Science ID 000324672700005
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MEMS-based shear characterization of soft hydrated samples
JOURNAL OF MICROMECHANICS AND MICROENGINEERING
2013; 23 (8)
View details for DOI 10.1088/0960-1317/23/8/085001
View details for Web of Science ID 000322221100003
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Nanomechanical Actuation of a Silicon Cantilever Using an Azo Dye, Self-Assembled Monolayer
LANGMUIR
2013; 29 (23): 7118-7124
Abstract
The emerging fields of nanomotors and optomechanics are based on the harnessing of light to generate force. However, our ability to detect small surface stresses is limited by temperature drift, environmental noise, and low-frequency flicker electronic noise. To address these limitations, we functionalized microfabricated silicon cantilevers with an azo dye, silane-based self-assembled monolayer and modulated the surface stress by exciting the optical switch with a 405-nm laser. Atomic force microscopy, contact angle analysis, ellipsometry, and X-ray photoelectron spectroscopy verified successful assembly of molecules on the cantilever. Ultraviolet and visible spectra demonstrate optical switching of the synthesized molecule in solution. By turning the laser on and off at a specific rate (e.g., 1 Hz), the cantilever deflection can be measured via Fourier techniques, thus separating the signal of interest from the noise. This technique empowers the design of highly sensitive surface stress measurements.
View details for DOI 10.1021/la3034676
View details for Web of Science ID 000320485400042
View details for PubMedID 23663108
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Integrated Multifunctional Environmental Sensors
JOURNAL OF MICROELECTROMECHANICAL SYSTEMS
2013; 22 (3): 779-793
View details for DOI 10.1109/JMEMS.2013.2245400
View details for Web of Science ID 000319827700030
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Spatially Resolved Study of Backscattering in the Quantum Spin Hall State
PHYSICAL REVIEW X
2013; 3 (2)
View details for DOI 10.1103/PhysRevX.3.021003
View details for Web of Science ID 000317918200001
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Spatial patterning of endothelium modulates cell morphology, adhesiveness and transcriptional signature
BIOMATERIALS
2013; 34 (12): 2928-2937
Abstract
Microscale and nanoscale structures can spatially pattern endothelial cells (ECs) into parallel-aligned organization, mimicking their cellular alignment in blood vessels exposed to laminar shear stress. However, the effects of spatial patterning on the function and global transcriptome of ECs are incompletely characterized. We used both parallel-aligned micropatterned and nanopatterned biomaterials to evaluate the effects of spatial patterning on the phenotype of ECs, based on gene expression profiling, functional characterization of monocyte adhesion, and quantification of cellular morphology. We demonstrate that both micropatterned and aligned nanofibrillar biomaterials could effectively guide EC organization along the direction of the micropatterned channels or nanofibrils, respectively. The ability of ECs to sense spatial patterning cues were abrogated in the presence of cytoskeletal disruption agents. Moreover, both micropatterned and aligned nanofibrillar substrates promoted an athero-resistant EC phenotype by reducing endothelial adhesiveness for monocytes and platelets, as well as by downregulating the expression of adhesion proteins and chemokines. We further found that micropatterned ECs have a transcriptional signature that is unique from non-patterned ECs, as well as from ECs aligned by shear stress. These findings highlight the importance of spatial patterning cues in guiding EC organization and function, which may have clinical relevance in the development of vascular grafts that promote patency.
View details for DOI 10.1016/j.biomaterials.2013.01.017
View details for Web of Science ID 000316038900008
View details for PubMedID 23357369
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Sacrificial layer technique for axial force post assay of immature cardiomyocytes
BIOMEDICAL MICRODEVICES
2013; 15 (1): 171-181
Abstract
Immature primary and stem cell-derived cardiomyocytes provide useful models for fundamental studies of heart development and cardiac disease, and offer potential for patient specific drug testing and differentiation protocols aimed at cardiac grafts. To assess their potential for augmenting heart function, and to gain insight into cardiac growth and disease, tissue engineers must quantify the contractile forces of these single cells. Currently, axial contractile forces of isolated adult heart cells can only be measured by two-point methods such as carbon fiber techniques, which cannot be applied to neonatal and stem cell-derived heart cells because they are more difficult to handle and lack a persistent shape. Here we present a novel axial technique for measuring the contractile forces of isolated immature cardiomyocytes. We overcome cell manipulation and patterning challenges by using a thermoresponsive sacrificial support layer in conjunction with arrays of widely separated elastomeric microposts. Our approach has the potential to be high-throughput, is functionally analogous to current gold-standard axial force assays for adult heart cells, and prescribes elongated cell shapes without protein patterning. Finally, we calibrate these force posts with piezoresistive cantilevers to dramatically reduce measurement error typical for soft polymer-based force assays. We report quantitative measurements of peak contractile forces up to 146 nN with post stiffness standard error (26 nN) far better than that based on geometry and stiffness estimates alone. The addition of sacrificial layers to future 2D and 3D cell culture platforms will enable improved cell placement and the complex suspension of cells across 3D constructs.
View details for DOI 10.1007/s10544-012-9710-3
View details for Web of Science ID 000313517800018
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Microactuator device for integrated measurement of epithelium mechanics
BIOMEDICAL MICRODEVICES
2013; 15 (1): 117-123
Abstract
Mechanical forces are among important factors that drive cellular function and organization. We present a microfabricated device with on-chip actuation for mechanical testing of single cells. An integrated immersible electrostatic actuator system is demonstrated that applies calibrated forces to cells. We conduct stretching experiments by directly applying forces to epithelial cells adhered to device surfaces functionalized with collagen. We measure mechanical properties including stiffness, hysteresis and visco-elasticity of adherent cells.
View details for DOI 10.1007/s10544-012-9693-0
View details for Web of Science ID 000313517800012
View details for PubMedID 22927158
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Characterization of the Biophysical Origins of Mechanical Homeostasis at Cellular Adhesions
CELL PRESS. 2013: 491A-491A
View details for Web of Science ID 000316074304489
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Abnormal Calcium Handling Properties Underlie Familial Hypertrophic Cardiomyopathy Pathology in Patient-Specific Induced Pluripotent Stem Cells
CELL STEM CELL
2013; 12 (1): 101-113
Abstract
Familial hypertrophic cardiomyopathy (HCM) is a prevalent hereditary cardiac disorder linked to arrhythmia and sudden cardiac death. While the causes of HCM have been identified as genetic mutations in the cardiac sarcomere, the pathways by which sarcomeric mutations engender myocyte hypertrophy and electrophysiological abnormalities are not understood. To elucidate the mechanisms underlying HCM development, we generated patient-specific induced pluripotent stem cell cardiomyocytes (iPSC-CMs) from a ten-member family cohort carrying a hereditary HCM missense mutation (Arg663His) in the MYH7 gene. Diseased iPSC-CMs recapitulated numerous aspects of the HCM phenotype including cellular enlargement and contractile arrhythmia at the single-cell level. Calcium (Ca(2+)) imaging indicated dysregulation of Ca(2+) cycling and elevation in intracellular Ca(2+) ([Ca(2+)](i)) are central mechanisms for disease pathogenesis. Pharmacological restoration of Ca(2+) homeostasis prevented development of hypertrophy and electrophysiological irregularities. We anticipate that these findings will help elucidate the mechanisms underlying HCM development and identify novel therapies for the disease.
View details for DOI 10.1016/j.stem.2012.10.010
View details for Web of Science ID 000313839500014
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MEMS-based force-clamp analysis of the role of body stiffness in C. elegans touch sensation
INTEGRATIVE BIOLOGY
2013; 5 (6): 853-864
Abstract
Touch is enabled by mechanoreceptor neurons in the skin and plays an essential role in our everyday lives, but is among the least understood of our five basic senses. Force applied to the skin deforms these neurons and activates ion channels within them. Despite the importance of the mechanics of the skin in determining mechanoreceptor neuron deformation and ultimately touch sensation, the role of mechanics in touch sensitivity is poorly understood. Here, we use the model organism Caenorhabditis elegans to directly test the hypothesis that body mechanics modulate touch sensitivity. We demonstrate a microelectromechanical system (MEMS)-based force clamp that can apply calibrated forces to freely crawling C. elegans worms and measure touch-evoked avoidance responses. This approach reveals that wild-type animals sense forces <1 μN and indentation depths <1 μm. We use both genetic manipulation of the skin and optogenetic modulation of body wall muscles to alter body mechanics. We find that small changes in body stiffness dramatically affect force sensitivity, while having only modest effects on indentation sensitivity. We investigate the theoretical body deformation predicted under applied force and conclude that local mechanical loads induce inward bending deformation of the skin to drive touch sensation in C. elegans.
View details for DOI 10.1039/c3ib20293c
View details for Web of Science ID 000319571600002
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Spontaneous cardiomyocyte differentiation of mouse embryoid bodies regulated by hydrogel crosslink density
Biomaterials Science
2013; 10 (1): 1082 - 1090
View details for DOI 10.1039/C3BM60139K
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The Yin-Yang of Rigidity Sensing: How Forces and Mechanical Properties Regulate the Cellular Response to Materials
ANNUAL REVIEW OF MATERIALS RESEARCH, VOL 43
2013; 43: 589-618
View details for DOI 10.1146/annurev-matsci-062910-100407
View details for Web of Science ID 000323892700023
- Microsystems AND Functional Assay for Mechanobiology 2013
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Spatial patterning of endothelium modulates cell morphology, adhesiveness and transcriptional signature
Biomaterials
2013; 34 (12): 2928-37
View details for DOI 10.1016/j.biomaterials.2013.01.017
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Spatially Resolved Study of Backscattering in the Quantum Spin Hall State
Physical Review X
2013; 3: 21003
View details for DOI 10.1103/PhysRevX.3.021003
- A Real Time Imaging System for Tracking Freely Moving C. elegans in Touch Assays 2013
- Ultra-Thin Atomic Layer Deposition Films for Corrosion Resistance 2013
- Inducing variations in the shortening of single cardiomyocytes with localized mechanical stimulation 2013
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The Yin-Yang of Rigidity Sensing: How Forces and Mechanical Properties Regulate the Cellular Response to Materials
Annual Review of Materials Research
2013
View details for DOI 10.1146/annurev-matsci-062910-100407
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MEMS-based force-clamp analysis of the role of body stiffness in C. elegans touch sensation
Integrative Biology
2013; 5 (6): 853-64
View details for DOI 10.1039/C3IB20293C
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MEMS-based shear characterization of soft hydrated samples
Journal of Micromechanics and Microengineering
2013; 8 (23): 85001
View details for DOI 10.1088/0960-1317/23/8/085001
- Planar patterned stretchable electrode arrays based on flexible printed circuits Journal of Micromechanics and Microengineering, 23, 105004 (2013) *Article chosen for IOP Select Distribution due to its novelty, significance and potential impact on future research 2013; 23: 105004
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Nanomechanical Actuation of a Silicon Cantilever Using an Azo Dye, Self-Assembled Monolayer
Langmuir
2013; 23 (29): 6779-7178
View details for DOI 10.1021/la3034676
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Spontaneous cardiomyocyte differentiation of mouse embryoid bodies regulated by hydrogel crosslink density
BIOMATERIALS SCIENCE
2013; 1 (10): 1082-1090
View details for DOI 10.1039/c3bm60139k
View details for Web of Science ID 000330137700009
- Integrated Sensor Cross-Sensitivity Analysis 2013
- Piezoresistor Design and Applications Springer. 2013
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PIEZORESISTIVE CANTILEVER PROBES FOR SIMULTANEOUS NANOSCALE TOPOGRAPHY AND CONDUCTIVITY IMAGING
26TH IEEE INTERNATIONAL CONFERENCE ON MICRO ELECTRO MECHANICAL SYSTEMS (MEMS 2013)
2013: 323-326
View details for Web of Science ID 000320549200083
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Formation of composite polyacrylamide and silicone substrates for independent control of stiffness and strain
LAB ON A CHIP
2013; 13 (4): 646-649
Abstract
Cells that line major tissues in the body such as blood vessels, lungs and gastrointestinal tract experience deformation from mechanical strain with our heartbeat, breathing, and other daily activities. Tissues also remodel in both development and disease, changing their mechanical properties. Taken together, cells can experience vastly different mechanical cues resulting from the combination of these interdependent stimuli. To date, most studies of cellular mechanotransduction have been limited to assays in which variations in substrate stiffness and strain were not combined. Here, we address this technological gap by implementing a method that can simultaneously tune both substrate stiffness and mechanical strain. Substrate stiffness is controlled with different monomer and crosslinker ratios during polyacrylamide gel polymerization, and strain is transferred from the underlying silicone platform when stretched. We demonstrate this platform with polyacrylamide gels with elastic moduli at 6 kPa and 20 kPa in combination with two different silicone formulations. The gels remain attached with up to 50% applied strains. To validate strain transfer through the gels into cells, we employ particle-tracking methods and observe strain transmission via cell morphological changes.
View details for DOI 10.1039/c2lc41110e
View details for Web of Science ID 000313971300019
View details for PubMedID 23287818
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Faster than the Speed of Hearing: Nanomechanical Force Probes Enable the Electromechanical Observation of Cochlear Hair Cells
NANO LETTERS
2012; 12 (12): 6107-6111
Abstract
Understanding the mechanisms responsible for our sense of hearing requires new tools for unprecedented stimulation and monitoring of sensory cell mechanotransduction at frequencies yet to be explored. We describe nanomechanical force probes designed to evoke mechanotransduction currents at up to 100 kHz in living cells. High-speed force and displacement metrology is enabled by integrating piezoresistive sensors and piezoelectric actuators onto nanoscale cantilevers. The design, fabrication process, actuator performance, and actuator-sensor crosstalk compensation results are presented. We demonstrate the measurement of mammalian cochlear hair cell mechanotransduction with simultaneous patch clamp recordings at unprecedented speeds. The probes can deliver mechanical stimuli with sub-10 ?s rise times in water and are compatible with standard upright and inverted microscopes.
View details for DOI 10.1021/nl3036349
View details for Web of Science ID 000312122100012
View details for PubMedID 23181721
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High-bandwidth piezoresistive force probes with integrated thermal actuation
IOP PUBLISHING LTD. 2012
View details for DOI 10.1088/0960-1317/22/9/095012
View details for Web of Science ID 000308210600022
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E-cadherin is under constitutive actomyosin-generated tension that is increased at cell-cell contacts upon externally applied stretch
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2012; 109 (31): 12568-12573
Abstract
Classical cadherins are transmembrane proteins at the core of intercellular adhesion complexes in cohesive metazoan tissues. The extracellular domain of classical cadherins forms intercellular bonds with cadherins on neighboring cells, whereas the cytoplasmic domain recruits catenins, which in turn associate with additional cytoskeleton binding and regulatory proteins. Cadherin/catenin complexes are hypothesized to play a role in the transduction of mechanical forces that shape cells and tissues during development, regeneration, and disease. Whether mechanical forces are transduced directly through cadherins is unknown. To address this question, we used a Förster resonance energy transfer (FRET)-based molecular tension sensor to test the origin and magnitude of tensile forces transmitted through the cytoplasmic domain of E-cadherin in epithelial cells. We show that the actomyosin cytoskeleton exerts pN-tensile force on E-cadherin, and that this tension requires the catenin-binding domain of E-cadherin and ?E-catenin. Surprisingly, the actomyosin cytoskeleton constitutively exerts tension on E-cadherin at the plasma membrane regardless of whether or not E-cadherin is recruited to cell-cell contacts, although tension is further increased at cell-cell contacts when adhering cells are stretched. Our findings thus point to a constitutive role of E-cadherin in transducing mechanical forces between the actomyosin cytoskeleton and the plasma membrane, not only at cell-cell junctions but throughout the cell surface.
View details for DOI 10.1073/pnas.1204390109
View details for Web of Science ID 000307538200062
View details for PubMedID 22802638
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Low-impedance shielded tip piezoresistive probe enables portable microwave impedance microscopy
MICRO & NANO LETTERS
2012; 7 (4): 321-324
View details for DOI 10.1049/mnl.2011.0679
View details for Web of Science ID 000303341600008
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SPECIAL SECTION: MICRO AND NANO TECHNOLOGIES FOR PROBE-BASED MICROSCOPY
MICRO & NANO LETTERS
2012; 7 (4): 296-296
View details for DOI 10.1049/mnl.2012.0244
View details for Web of Science ID 000303341600001
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Hydrogel crosslinking density regulates temporal contractility of human embryonic stem cell-derived cardiomyocytes in 3D cultures
SOFT MATTER
2012; 8 (39): 10141-10148
Abstract
Systematically tunable in vitro platforms are invaluable in gaining insight to stem cell-microenvironment interactions in three-dimensional cultures. Utilizing recombinant protein technology, we independently tune hydrogel properties to systematically isolate the effects of matrix crosslinking density on cardiomyocyte differentiation, maturation, and function. We show that contracting human embryonic stem cell-derived cardiomyocytes (hESC-CMs) remain viable within four engineered elastin-like hydrogels of varying crosslinking densities with elastic moduli ranging from 0.45 to 2.4 kPa. Cardiomyocyte phenotype and function was maintained within hESC embryoid bodies for up to 2 weeks. Interestingly, increased crosslinking density was shown to transiently suspend spontaneous contractility. While encapsulated cells began spontaneous contractions at day 1 in hydrogels of the lowest crosslinking density, onset of contraction was increasingly delayed at higher crosslinking densities up to 6 days. However, once spontaneous contraction was restored, the rate of contraction was similar within all materials (71 ± 8 beats/min). Additionally, all groups successfully responded to electrical pacing at both 1 and 2 Hz. This study demonstrates that encapsulated hESC-CMs respond to 3D matrix crosslinking density within elastin-like hydrogels and stresses the importance of investigating temporal cellular responses in 3D cultures.
View details for DOI 10.1039/c2sm26082d
View details for Web of Science ID 000308882800024
- Influence of body mechanics on force thresholds for touch sensation in C. elegans 2012
- Body mechanics regulate the force threshold for gentle touch sensation in the nematode C. elegans 2012
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Low-Impedance Shielded Tip Piezoresistive Probe Enables Portable Microwave Impedance Microscopy
Micro & Nano Letters
2012; 7 (4): 321–324
View details for DOI 10.1049/mnl.2011.0679
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Sacrificial layer technique for axial force post assay of immature cardiomyocytes
Biomedical Microdevices
2012; 15 (1): 171-181
View details for DOI 10.1007/s10544-012-9710-3
- Covalent Attachment of Bioactive Molecules to PDMS for Cardiomyocyte Adhesion 2012
- Effects of substrate mechanics on contractility of cardiomyocytes generated from human pluripotent stem cells International Journal of Cell Biology 2012: 508294
- High bandwidth piezoresistive force probes with integrated thermal actuation Journal of Micromechanics and Microengineering 2012; 22 (9): 95012
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Formation of composite polyacrylamide and silicone substrates for independent control of stiffness and strain
Lab Chip
2012; 13: 646-649
View details for DOI 10.1039/C2LC41110E
- Piezoresistive Cantilevers for Biological Force Measurements 2012
- MEMS force probes for cell mechanobiology at the microsecond scale 2012
- Changes in Cell Traction Forces in Response to Uniaxial Loading 2012
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MULTI-FUNCTIONAL INTEGRATED SENSORS FOR THE ENVIRONMENT
2012 IEEE 25TH INTERNATIONAL CONFERENCE ON MICRO ELECTRO MECHANICAL SYSTEMS (MEMS)
2012
View details for Web of Science ID 000312912800038
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UNIAXIAL CELL STRETCHER ENABLES HIGH RESOLUTION LIVE CELL IMAGING
2012 IEEE 25TH INTERNATIONAL CONFERENCE ON MICRO ELECTRO MECHANICAL SYSTEMS (MEMS)
2012
View details for Web of Science ID 000312912800215
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LOW-IMPEDANCE SHIELDED TIP PIEZORESISTIVE PROBE ENABLES PORTABLE MICROWAVE IMPEDANCE MICROSCOPY
IEEE. 2012
View details for Web of Science ID 000312912800070
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High bandwidth piezoresistive force probes with integrated thermal actuation.
Journal of micromechanics and microengineering : structures, devices, and systems
2012; 22 (9)
Abstract
We present high-speed force probes with on-chip actuation and sensing for the measurement of pN-scale forces at the microsecond time scale. We achieve a high resonant frequency in water (1-100 kHz) with requisite low spring constants (0.3-40 pN/nm) and low integrated force noise (1-100 pN) by targeting probe dimensions on the order of 300 nm thick, 1-2 ?m wide and 30-200 ?m long. Forces are measured using silicon piezoresistors while the probes are actuated thermally with an aluminum unimorph and silicon heater. The piezoresistive sensors are designed using open source numerical optimization code that incorporates constraints on operating temperature. Parylene passivation enables operation in ionic media and we demonstrate simultaneous actuation and sensing. The improved design and fabrication techniques that we describe enable a 10-20 fold improvement in force resolution or measurement bandwidth over prior piezoresistive cantilevers of comparable thickness.
View details for PubMedID 23175616
- Low-Impedance Shielded Tip Piezoresistive Probe Enables Portable Microwave Impedance Microscopy Micro Nano Letters 2012; 7 (4): 321?324
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Effects of substrate mechanics on contractility of cardiomyocytes generated from human pluripotent stem cells.
International journal of cell biology
2012; 2012: 508294-?
Abstract
Human pluripotent stem cell (hPSC-) derived cardiomyocytes have potential applications in drug discovery, toxicity testing, developmental studies, and regenerative medicine. Before these cells can be reliably utilized, characterization of their functionality is required to establish their similarity to native cardiomyocytes. We tracked fluorescent beads embedded in 4.4-99.7?kPa polyacrylamide hydrogels beneath contracting neonatal rat cardiomyocytes and cardiomyocytes generated from hPSCs via growth-factor-induced directed differentiation to measure contractile output in response to changes in substrate mechanics. Contraction stress was determined using traction force microscopy, and morphology was characterized by immunocytochemistry for ?-actinin and subsequent image analysis. We found that contraction stress of all types of cardiomyocytes increased with substrate stiffness. This effect was not linked to beating rate or morphology. We demonstrated that hPSC-derived cardiomyocyte contractility responded appropriately to isoprenaline and remained stable in culture over a period of 2 months. This study demonstrates that hPSC-derived cardiomyocytes have appropriate functional responses to substrate stiffness and to a pharmaceutical agent, which motivates their use in further applications such as drug evaluation and cardiac therapies.
View details for DOI 10.1155/2012/508294
View details for PubMedID 22649451
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Microsystems for biomimetic stimulation of cardiac cells
LAB ON A CHIP
2012; 12 (18): 3235-3248
Abstract
The heart is a complex integrated system that leverages mechanoelectrical signals to synchronize cardiomyocyte contraction and push blood throughout the body. The correct magnitude, timing, and distribution of these signals is critical for proper functioning of the heart; aberrant signals can lead to acute incidents, long-term pathologies, and even death. Due to the heart's limited regenerative capacity and the wide variety of pathologies, heart disease is often studied in vitro. However, it is difficult to accurately replicate the cardiac environment outside of the body. Studying the biophysiology of the heart in vitro typically consists of studying single cells in a tightly controlled static environment or whole tissues in a complex dynamic environment. Micro-electromechanical systems (MEMS) allow us to bridge these two extremes by providing increasing complexity for cell culture without having to use a whole tissue. Here, we carefully describe the electromechanical environment of the heart and discuss MEMS specifically designed to replicate these stimulation modes. Strengths, limitations and future directions of various designs are discussed for a variety of applications.
View details for DOI 10.1039/c2lc40308k
View details for Web of Science ID 000307583400002
View details for PubMedID 22782590
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DEG/ENaC but Not TRP Channels Are the Major Mechanoelectrical Transduction Channels in a C. elegans Nociceptor
NEURON
2011; 71 (5): 845-857
Abstract
Many nociceptors detect mechanical cues, but the ion channels responsible for mechanotransduction in these sensory neurons remain obscure. Using in vivo recordings and genetic dissection, we identified the DEG/ENaC protein, DEG-1, as the major mechanotransduction channel in ASH, a polymodal nociceptor in Caenorhabditis elegans. But DEG-1 is not the only mechanotransduction channel in ASH: loss of deg-1 revealed a minor current whose properties differ from those expected of DEG/ENaC channels. This current was independent of two TRPV channels expressed in ASH. Although loss of these TRPV channels inhibits behavioral responses to noxious stimuli, we found that both mechanoreceptor currents and potentials were essentially wild-type in TRPV mutants. We propose that ASH nociceptors rely on two genetically distinct mechanotransduction channels and that TRPV channels contribute to encoding and transmitting information. Because mammalian and insect nociceptors also coexpress DEG/ENaCs and TRPVs, the cellular functions elaborated here for these ion channels may be conserved.
View details for DOI 10.1016/j.neuron.2011.06.038
View details for Web of Science ID 000294877900010
View details for PubMedID 21903078
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Patterned cracks improve yield in the release of compliant microdevices from silicon-on-insulator wafers
JOURNAL OF MICROMECHANICS AND MICROENGINEERING
2011; 21 (8)
View details for DOI 10.1088/0960-1317/21/8/087001
View details for Web of Science ID 000293163700038
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Self-heating in piezoresistive cantilevers
APPLIED PHYSICS LETTERS
2011; 98 (22)
View details for DOI 10.1063/1.3595485
View details for Web of Science ID 000291405700053
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Stretchable microelectrode array using room-temperature liquid alloy interconnects
JOURNAL OF MICROMECHANICS AND MICROENGINEERING
2011; 21 (5)
View details for DOI 10.1088/0960-1317/21/5/054015
View details for Web of Science ID 000289986600016
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Integrated strain array for cellular mechanobiology studies
JOURNAL OF MICROMECHANICS AND MICROENGINEERING
2011; 21 (5)
View details for DOI 10.1088/0960-1317/21/5/054016
View details for Web of Science ID 000289986600017
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Calibrated micropost arrays for biomechanical characterisation of cardiomyocytes
MICRO & NANO LETTERS
2011; 6 (5): 317-322
View details for DOI 10.1049/mnl.2011.0031
View details for Web of Science ID 000290764000007
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MEMS in biology and medicine
JOURNAL OF MICROMECHANICS AND MICROENGINEERING
2011; 21 (5)
View details for DOI 10.1088/0960-1317/21/5/050201
View details for Web of Science ID 000289986600001
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Caenorhabditis elegans Body Mechanics Are Regulated by Body Wall Muscle Tone
BIOPHYSICAL JOURNAL
2011; 100 (8): 1977-1985
Abstract
Body mechanics in the nematode Caenorhabditis elegans are central to both mechanosensation and locomotion. Previous work revealed that the mechanics of the outer shell, rather than internal hydrostatic pressure, dominates stiffness. This shell is comprised of the cuticle and the body wall muscles, either of which could contribute to the body mechanics. Here, we tested the hypothesis that the muscles are an important contributor by modulating muscle tone using optogenetic and pharmacological tools, and measuring animal stiffness using piezoresistive microcantilevers. As a proxy for muscle tone, we measured changes in animal length under the same treatments. We found that treatments that induce muscle contraction generally resulted in body shortening and stiffening. Conversely, methods to relax the muscles more modestly increased length and decreased stiffness. The results support the idea that body wall muscle activation contributes significantly to and can modulate C. elegans body mechanics. Modulation of body stiffness would enable nematodes to tune locomotion or swimming gaits and may have implications in touch sensation.
View details for DOI 10.1016/j.bpj.2011.02.035
View details for Web of Science ID 000289864100017
View details for PubMedID 21504734
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Piezoresistive cantilever force-clamp system
REVIEW OF SCIENTIFIC INSTRUMENTS
2011; 82 (4)
Abstract
We present a microelectromechanical device-based tool, namely, a force-clamp system that sets or "clamps" the scaled force and can apply designed loading profiles (e.g., constant, sinusoidal) of a desired magnitude. The system implements a piezoresistive cantilever as a force sensor and the built-in capacitive sensor of a piezoelectric actuator as a displacement sensor, such that sample indentation depth can be directly calculated from the force and displacement signals. A programmable real-time controller operating at 100 kHz feedback calculates the driving voltage of the actuator. The system has two distinct modes: a force-clamp mode that controls the force applied to a sample and a displacement-clamp mode that controls the moving distance of the actuator. We demonstrate that the system has a large dynamic range (sub-nN up to tens of ?N force and nm up to tens of ?m displacement) in both air and water, and excellent dynamic response (fast response time, <2 ms and large bandwidth, 1 Hz up to 1 kHz). In addition, the system has been specifically designed to be integrated with other instruments such as a microscope with patch-clamp electronics. We demonstrate the capabilities of the system by using it to calibrate the stiffness and sensitivity of an electrostatic actuator and to measure the mechanics of a living, freely moving Caenorhabditis elegans nematode.
View details for DOI 10.1063/1.3574362
View details for Web of Science ID 000290051500022
View details for PubMedID 21529009
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Effects of substrate mechanics on yield and contractility of cardiomyocytes generated from pluripotent stem cells
AMER CHEMICAL SOC. 2011
View details for Web of Science ID 000291982801875
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Self-heating in piezoresistive cantilevers.
Applied physics letters
2011; 98 (22): 223103
Abstract
We report experiments and models of self-heating in piezoresistive microcantilevers that show how cantilever measurement resolution depends on the thermal properties of the surrounding fluid. The predicted cantilever temperature rise from a finite difference model is compared with detailed temperature measurements on fabricated devices. Increasing the fluid thermal conductivity allows for lower temperature operation for a given power dissipation, leading to lower force and displacement noise. The force noise in air is 76% greater than in water for the same increase in piezoresistor temperature.
View details for PubMedID 21731884
- Stretchable microelectrode array using room-temperature-liquid alloy interconnects JMM 2011; 5 (21): 54015
- The functional importance of the MEC-4 transmembrane domain in force activation of the channel 2011
- Micropost-based Functional Assay of Adult Heart Cells: Does Mechanosensing Limit Force Production? 2011
- Integrated strain array for cellular mechanobiology studies Integrated strain array for cellular mechanobiology studies JMM 2011; 5 (21): 54016
- Calibrated micropost arrays for biomechanical characterization of cardiomyocytes Micro and Nano Letters 2011; 5 (6): 317-322
- Parametric Analysis of Strain Effects on Cell-Cell Junctions 2011
- Adhesion Proteins for Mechanotransduction Assays 2011
- Tools for studying biomechanical interactions in cells in Mechanobiology of Cell-Cell and Cell-Matrix Interactions Handbook Springer. 2011
- The MEMS Design Process in Handbook of MEMS Materials and Processes Springer. 2011
- Piezoresistive cantilever force-clamp system Review of Scientific Instruments 2011; 82 (4): 43703
- Characterization of Adhesion Proteins for Cell Mechanotransduction Assays 2011
- An Electrically-Addressable, Liquid Release Well Array for a Hand-held, Scent Dispense System Micro Nano Lett. 2011; 6 (1): 37–38
- Media:Hill_2011_JMM.pdf|Patterned cracks improve yield in the release of compliant microdevices from silicon-on-insulator wafers Journal of Micromechanics and Microengineering 2011; 21
- Self-sensing, coaxial-tip piezoresistive probes for scanning gate and microwave microscopy 2011
- DEG/ENaC but not TRP Channels are the major mechanoelectrical transduction channels in a C. elegans nociceptor Neuron 2011; 71 (5)
- Effects of crosslinking density on viability and maintenance of human embryonic stem cell-derived cardiomyocytes in elastin-like hydrogels 2011
- Self-heating in piezoresistive cantilevers Applied Physics Letters 2011; 98 (22)
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PATTERNED CRACKS IN THE BURIED OXIDE LAYER IMPROVE YIELD IN DEVICE RELEASE FROM SOI WAFERS
2011 IEEE 24TH INTERNATIONAL CONFERENCE ON MICRO ELECTRO MECHANICAL SYSTEMS (MEMS)
2011: 300-303
View details for Web of Science ID 000295841200075
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New Devices for Investigating Hair Cell Mechanical Properties
WHAT FIRE IS IN MINE EARS: PROGRESS IN AUDITORY BIOMECHANICS
2011; 1403
View details for DOI 10.1063/1.3658054
View details for Web of Science ID 000301945200003
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Electrically addressable, liquid release well array for a hand-held, scent-dispense system
MICRO & NANO LETTERS
2011; 6 (1): 37-38
View details for DOI 10.1049/mnl.2010.0144
View details for Web of Science ID 000285921300010
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Integrated strain array for cellular mechanobiology studies.
Journal of micromechanics and microengineering : structures, devices, and systems
2011; 21 (5): 54016-54025
Abstract
We have developed an integrated strain array for cell culture enabling high-throughput mechano-transduction studies. Biocompatible cell culture chambers were integrated with an acrylic pneumatic compartment and microprocessor-based control system. Each element of the array consists of a deformable membrane supported by a cylindrical pillar within a well. For user-prescribed waveforms, the annular region of the deformable membrane is pulled into the well around the pillar under vacuum, causing the pillar-supported region with cultured cells to be stretched biaxially. The optically clear device and pillar-based mechanism of operation enables imaging on standard laboratory microscopes. Straightforward fabrication utilizes off-the-shelf components, soft lithography techniques in polydimethylsiloxane, and laser ablation of acrylic sheets. Proof of compatibility with basic biological assays and standard imaging equipment were accomplished by straining C2C12 skeletal myoblast cells on the device for 6 hours. At higher strains, cells and actin stress fibers realign with a circumferential preference.
View details for PubMedID 21857773
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Design of piezoresistive versus piezoelectric contact mode scanning probes
JOURNAL OF MICROMECHANICS AND MICROENGINEERING
2010; 20 (9)
View details for DOI 10.1088/0960-1317/20/9/095023
View details for Web of Science ID 000281398800023
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Strain array for cell culture: cyclic strain affects epithelial cell spreading
FEDERATION AMER SOC EXP BIOL. 2010
View details for Web of Science ID 000208675501606
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Aluminum nitride on titanium for CMOS compatible piezoelectric transducers
JOURNAL OF MICROMECHANICS AND MICROENGINEERING
2010; 20 (2)
View details for DOI 10.1088/0960-1317/20/2/025008
View details for Web of Science ID 000275331200010
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Role of surface roughness in hysteresis during adhesive elastic contact
PHILOSOPHICAL MAGAZINE LETTERS
2010; 90 (12): 891-902
Abstract
In experiments that involve contact with adhesion between two surfaces, as found in atomic force microscopy or nanoindentation, two distinct contact force (P) vs. indentation-depth (h) curves are often measured depending on whether the indenter moves towards or away from the sample. The origin of this hysteresis is not well understood and is often attributed to moisture, plasticity or viscoelasticity. Here we report experiments that show that hysteresis can exist in the absence of these effects, and that its magnitude depends on surface roughness. We develop a theoretical model in which the hysteresis appears as the result of a series of surface instabilities, in which the contact area grows or recedes by a finite amount. The model can be used to estimate material properties from contact experiments even when the measured P-h curves are not unique.
View details for DOI 10.1080/09500839.2010.521204
View details for Web of Science ID 000283319100005
View details for PubMedID 21152108
- Force sensing optimization and applications book chapter in Advanced Materials and Technologies for Micro/Nano-Devices, Sensors and Actuators Springer. 2010
- Microfabricated calibration tool for direct shear stiffness measurements with applications in cell mechanics 2010
- Parametric Analysis of Cyclic Strain Effects on Cell-cell Adhesions 2010
- Parametric analysis of cyclic strain effects on cell-cell adhesions 2010
- Piezoresistive cantilevers optimized for kilohertz force sensing in aqueous solutions 2010
- Development of 3-dimesional Test Beds to Investigate Cell Matrix Interactions in vitro 2010
- Micromechanical Environments for Imaging Mechanobiology 2010
- Behavioral Thresholds for Force-sensation Determined by an Integrated Video Tracking and Force-clamp System 2010
- Piezoresistive cantilever performance, part II: optimization Journal of Microelectromechanical Systems 2010; 19 (1): 149 - 161
- Role of surface roughness in hysteresis during adhesive elastic contact Philosophical Magazine Letters 2010
- The Contribution of Body Wall Muscles to C. Elegans Body Mechanics Determined Using Piezoresistive Microcantilevers 2010
- Self-Assembling Single Cells Across Microposts: First Axial Force Measurements in Immature Cardiomyocytes 2010
- Design of Piezoresistive vs. Piezoelectric Contact Mode Scanning Probes Journal of Micromechanics and Microengineering, 2010
- Microcantilever Force-Clamp and Optogenetics to Evaluate the Role of Body Mechanics in C. elegans Touch Sensation 2010
- Cardiomyocyte Suspension Bridges: First Measurements of Axial Force-Generation in Single Immature Heart Cells 2010
- Aluminum Nitride on Titanium for CMOS Compatible Piezoelectric Transducers Journal of Micromechanics and Microengineering 2010; 20: 25008
- Novel MEMS System for Calibrating Traction Force Substrates for Cell Culture 2010
- Piezoresistive cantilever performance, part I: analytical model for sensitivity Journal of Microelectromechanical Systems 2010; 19 (1): 137 - 148
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FORCE SENSING OPTIMIZATION AND APPLICATIONS
ADVANCED MATERIALS AND TECHNOLOGIES FOR MICRO/NANO-DEVICES, SENSORS AND ACTUATORS
2010: 287-298
View details for DOI 10.1007/978-90-481-3807-4_23
View details for Web of Science ID 000280184600023
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COAXIAL TIP PIEZORESISTIVE SCANNING PROBES FOR HIGH-RESOLUTION ELECTRICAL IMAGING
IEEE. 2010: 344-347
View details for Web of Science ID 000278416400084
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Optimization with Process Limits and Application Requirements for Force Sensors
2010 IEEE SENSORS
2010: 1946-1949
View details for Web of Science ID 000287982100427
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Coaxial Tip Piezoresistive Scanning Probes with Sub-Nanometer Vertical Displacement Resolution
IEEE. 2010: 1962-1966
View details for Web of Science ID 000287982100431
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Piezoresistive Cantilever Performance-Part I: Analytical Model for Sensitivity.
Journal of microelectromechanical systems : a joint IEEE and ASME publication on microstructures, microactuators, microsensors, and microsystems
2010; 19 (1): 137-148
Abstract
An accurate analytical model for the change in resistance of a piezoresistor is necessary for the design of silicon piezoresistive transducers. Ion implantation requires a high-temperature oxidation or annealing process to activate the dopant atoms, and this treatment results in a distorted dopant profile due to diffusion. Existing analytical models do not account for the concentration dependence of piezoresistance and are not accurate for nonuniform dopant profiles. We extend previous analytical work by introducing two nondimensional factors, namely, the efficiency and geometry factors. A practical benefit of this efficiency factor is that it separates the process parameters from the design parameters; thus, designers may address requirements for cantilever geometry and fabrication process independently. To facilitate the design process, we provide a lookup table for the efficiency factor over an extensive range of process conditions. The model was validated by comparing simulation results with the experimentally determined sensitivities of piezoresistive cantilevers. We performed 9200 TSUPREM4 simulations and fabricated 50 devices from six unique process flows; we systematically explored the design space relating process parameters and cantilever sensitivity. Our treatment focuses on piezoresistive cantilevers, but the analytical sensitivity model is extensible to other piezoresistive transducers such as membrane pressure sensors.
View details for PubMedID 20336183
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Piezoresistive Cantilever Performance-Part II: Optimization.
Journal of microelectromechanical systems : a joint IEEE and ASME publication on microstructures, microactuators, microsensors, and microsystems
2010; 19 (1): 149-161
Abstract
Piezoresistive silicon cantilevers fabricated by ion implantation are frequently used for force, displacement, and chemical sensors due to their low cost and electronic readout. However, the design of piezoresistive cantilevers is not a straightforward problem due to coupling between the design parameters, constraints, process conditions, and performance. We systematically analyzed the effect of design and process parameters on force resolution and then developed an optimization approach to improve force resolution while satisfying various design constraints using simulation results. The combined simulation and optimization approach is extensible to other doping methods beyond ion implantation in principle. The optimization results were validated by fabricating cantilevers with the optimized conditions and characterizing their performance. The measurement results demonstrate that the analytical model accurately predicts force and displacement resolution, and sensitivity and noise tradeoff in optimal cantilever performance. We also performed a comparison between our optimization technique and existing models and demonstrated eight times improvement in force resolution over simplified models.
View details for PubMedID 20333323
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Aluminum nitride on titanium for CMOS compatible piezoelectric transducers.
Journal of micromechanics and microengineering : structures, devices, and systems
2010; 20 (2): 25008
Abstract
Piezoelectric materials are widely used for microscale sensors and actuators but can pose material compatibility challenges. This paper reports a post-CMOS compatible fabrication process for piezoelectric sensors and actuators on silicon using only standard CMOS metals. The piezoelectric properties of aluminum nitride (AlN) deposited on titanium (Ti) by reactive sputtering are characterized and microcantilever actuators are demonstrated. The film texture of the polycrystalline Ti and AlN films is improved by removing the native oxide from the silicon substrate in situ and sequentially depositing the films under vacuum to provide a uniform growth surface. The piezoelectric properties for several AlN film thicknesses are measured using laser doppler vibrometry on unpatterned wafers and released cantilever beams. The film structure and properties are shown to vary with thickness, with values of d(33f), d(31) and d(33) of up to 2.9, -1.9 and 6.5 pm V(-1), respectively. These values are comparable with AlN deposited on a Pt metal electrode, but with the benefit of a fabrication process that uses only standard CMOS metals.
View details for PubMedID 20333316
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Sidewall epitaxial piezoresistor process and characterisation for in-plane force sensing applications
MICRO & NANO LETTERS
2009; 4 (4): 204-209
View details for DOI 10.1049/mnl.2009.0075
View details for Web of Science ID 000273047200005
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Design optimization of piezoresistive cantilevers for force sensing in air and water
JOURNAL OF APPLIED PHYSICS
2009; 106 (6)
View details for DOI 10.1063/1.3224965
View details for Web of Science ID 000270378100128
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Modeling and characterization of electrostatic comb-drive actuators in conducting liquid media
JOURNAL OF MICROMECHANICS AND MICROENGINEERING
2009; 19 (6)
View details for DOI 10.1088/0960-1317/19/6/065008
View details for Web of Science ID 000266287200008
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SU-8 force sensing pillar arrays for biological measurements
LAB ON A CHIP
2009; 9 (10): 1449-1454
Abstract
The generation and sensation of mechanical force plays a role in many dynamic biological processes, including touch sensation. This paper presents a two-axis micro strain gauge force sensor constructed from multiple layers of SU-8 and metal on quartz substrates. The sensor was designed to meet requirements for measuring tactile sensitivity and interaction forces exerted during locomotion by small organisms such as the nematode Caenorhabditis elegans. The device is transparent and compatible with light microscopes, allowing behavioral experiments to be combined with quantitative force measurements. For the first time, we have characterized the scale of interaction forces generated in wild-type C. elegans in probing and responding to their environment during locomotion. The device features sub-microN force resolution from 1 Hz to 1 kHz, >25 microN range, kHz acquisition rates and biocompatibility.
View details for DOI 10.1039/b818622g
View details for Web of Science ID 000268227400019
View details for PubMedID 19417913
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MEMS Electrostatic Actuation in Conducting Biological Media
JOURNAL OF MICROELECTROMECHANICAL SYSTEMS
2009; 18 (2): 405-413
Abstract
We present design and experimental implementation of electrostatic comb-drive actuators in solutions of high conductivity relevant for biological cells. The actuators are operated in the frequency range 1-10 MHz in ionic and biological cell culture media, with ionic strengths up to 150 mMoles/L. Typical displacement is 3.5 ?m at an applied peak-to-peak signal of 5V. Two different actuation schemes are presented and tested for performance at high frequency. A differential drive design is demonstrated to overcome the attenuation due to losses in parasitic impedances. The frequency dependence of the electrostatic force has been characterized in media of different ionic strengths. Circuit models for the electric double layer phenomena are used to understand and predict the actuator behavior. The actuator is integrated into a planar force sensing system to measure the stiffness of cells cultured on suspended structures.
View details for DOI 10.1109/JMEMS.2009.2013398
View details for Web of Science ID 000265090300018
View details for PubMedID 20161046
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Review: Semiconductor Piezoresistance for Microsystems
PROCEEDINGS OF THE IEEE
2009; 97 (3): 513-552
Abstract
Piezoresistive sensors are among the earliest micromachined silicon devices. The need for smaller, less expensive, higher performance sensors helped drive early micromachining technology, a precursor to microsystems or microelectromechanical systems (MEMS). The effect of stress on doped silicon and germanium has been known since the work of Smith at Bell Laboratories in 1954. Since then, researchers have extensively reported on microscale, piezoresistive strain gauges, pressure sensors, accelerometers, and cantilever force/displacement sensors, including many commercially successful devices. In this paper, we review the history of piezoresistance, its physics and related fabrication techniques. We also discuss electrical noise in piezoresistors, device examples and design considerations, and alternative materials. This paper provides a comprehensive overview of integrated piezoresistor technology with an introduction to the physics of piezoresistivity, process and material selection and design guidance useful to researchers and device engineers.
View details for DOI 10.1109/JPROC.2009.2013612
View details for Web of Science ID 000265092700006
View details for PubMedID 20198118
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Design optimization of piezoresistive cantilevers for force sensing in air and water.
Journal of applied physics
2009; 106 (6): 64310
Abstract
Piezoresistive cantilevers fabricated from doped silicon or metal films are commonly used for force, topography, and chemical sensing at the micro- and macroscales. Proper design is required to optimize the achievable resolution by maximizing sensitivity while simultaneously minimizing the integrated noise over the bandwidth of interest. Existing analytical design methods are insufficient for modeling complex dopant profiles, design constraints, and nonlinear phenomena such as damping in fluid. Here we present an optimization method based on an analytical piezoresistive cantilever model. We use an existing iterative optimizer to minimimize a performance goal, such as minimum detectable force. The design tool is available as open source software. Optimal cantilever design and performance are found to strongly depend on the measurement bandwidth and the constraints applied. We discuss results for silicon piezoresistors fabricated by epitaxy and diffusion, but the method can be applied to any dopant profile or material which can be modeled in a similar fashion or extended to other microelectromechanical systems.
View details for PubMedID 19865512
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A STRETCHABLE CELL CULTURE PLATFORM WITH EMBEDDED ELECTRODE ARRAY
IEEE 22ND INTERNATIONAL CONFERENCE ON MICRO ELECTRO MECHANICAL SYSTEMS (MEMS 2009)
2009: 407-410
View details for Web of Science ID 000341431500102
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PIEZORESISTIVE CANTILEVER-BASED FORCE-CLAMP SYSTEM FOR THE STUDY OF MECHANOTRANSDUCTION IN C. ELEGANS
IEEE 22ND INTERNATIONAL CONFERENCE ON MICRO ELECTRO MECHANICAL SYSTEMS (MEMS 2009)
2009: 188-191
View details for Web of Science ID 000341431500047
- A Stretchable Cell Culture Platform with Embedded Electrode Array 2009
- MEMS Electrostatic Actuation in Conducting Biological Media Journal of Microelectromechanical Systems 2009; 18 (2): 405 - 413
- Modeling and Characterization of Electrostatic Comb-drive Actuators in Conducting Liquid Media Journal Micromechanics and Microengineering 2009; 19: 65008
- Piezoresistive Cantilever Optimization and Applications invited paper, Materials Research Society Fall Meeting 2009
- Design optimization of piezoresistive cantilevers for force sensing in air and water Journal of Applied Physics 2009; 106 (6): 64310
- The Contribution of Body Wall Muscles to C. elegans Body Mechanics Determined Using Piezoresistive Microcantilevers 2009
- Synchronized Mechanical and Electrical Stimulation of Primary Heart Cells with a Stretchable Microelectrode Array 2009
- Strain Array for Cell Culture 2009
- Semiconductor Piezoresistance for Microsystems 2009
- Piezoresistive Cantilever-based Force clamp System for the Study of Mechanotransduction in C. elegans 2009
- On-chip Micromechanical Testing System for Studying Cell Mechanics 2009
- Measuring Thresholds for Touch Sensation in C. elegans 2009
- A High d33 CMOS Compatible Process for Aluminum Nitride on Titanium 2009
- Sidewall epitaxial piezoresistor process and characterization for in-plane force sensing applications Micro and Nano Letters 2009; 4 (4): 204-209
- High Frequency Force Sensing with Piezoresistive Cantilevers 2009
- Nano and the Future of Endovascular Medicine Endovascular Today, supp. 2009: 27-31
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Modeling and Characterization of Electrostatic Comb-drive Actuators in Conducting Liquid Media.
Journal of micromechanics and microengineering : structures, devices, and systems
2009; 19 (6): 1-9
Abstract
Operation of electrostatic actuators in liquid media has various proposed applications, especially in biological environments. The devices are operated by modulating at a frequency higher than the relaxation rate of the ions in solution. We present circuit models based on electric double layer theories to obtain analytical expression for the frequency-dependent force response of electrostatic actuators in ionic media. The model has been compared with experimental measurements of actuation in media of conductivity spanning five orders of magnitude. Further, impedance spectroscopy is used to measure the values of the circuit models, which are compared with the experiments. These measurements also quantify the parasitic impedances in the devices. A conformal layer of Parylene-C is demonstrated as a passivation scheme for the electrodes in corrosive media. The heating effects due to parasitic impedances are also quantified by temperature measurements of devices in fluids.
View details for PubMedID 20160927
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Artificial dirt: Microfluidic substrates for nematode neurobiology and behavior
JOURNAL OF NEUROPHYSIOLOGY
2008; 99 (6): 3136-3143
Abstract
With a nervous system of only 302 neurons, the free-living nematode Caenorhabditis elegans is a powerful experimental organism for neurobiology. However, the laboratory substrate commonly used in C. elegans research, a planar agarose surface, fails to reflect the complexity of this organism's natural environment, complicates stimulus delivery, and is incompatible with high-resolution optophysiology experiments. Here we present a new class of microfluidic devices for C. elegans neurobiology and behavior: agarose-free, micron-scale chambers and channels that allow the animals to crawl as they would on agarose. One such device mimics a moist soil matrix and facilitates rapid delivery of fluid-borne stimuli. A second device consists of sinusoidal channels that can be used to regulate the waveform and trajectory of crawling worms. Both devices are thin and transparent, rendering them compatible with high-resolution microscope objectives for neuronal imaging and optical recording. Together, the new devices are likely to accelerate studies of the neuronal basis of behavior in C. elegans.
View details for Web of Science ID 000256632600035
View details for PubMedID 18337372
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Suspension of nanoparticles in SU-8: Processing and characterization of nanocomposite polymers
ELSEVIER SCI LTD. 2008: 228-236
View details for DOI 10.1016/j.mejo.2007.05.012
View details for Web of Science ID 000253562400010
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Low 1/f noise, full bridge, microcantilever with longitudinal and transverse piezoresistors
APPLIED PHYSICS LETTERS
2008; 92 (3)
View details for DOI 10.1063/1.2825466
View details for Web of Science ID 000252718600076
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Sidewall epitaxial piezoresistor process for in-plane sensing applications
MEMS 2008: 21ST IEEE INTERNATIONAL CONFERENCE ON MICRO ELECTRO MECHANICAL SYSTEMS, TECHNICAL DIGEST
2008: 331-334
View details for Web of Science ID 000253356900083
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Application of a modified quality function deployment method for MEMS
INTERNATIONAL MECHANICAL ENGINEERING CONGRESS AND EXPOSITION 2007, VOL 11 PT A AND PT B: MICRO AND NANO SYSTEMS
2008: 159-168
View details for Web of Science ID 000254834900023
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Vapor-venting, micromachined heat exchanger for electronics cooling
PROCEEDINGS OF THE ASME INTERNATIONAL MECHANICAL ENGINEERING CONGRESS AND EXPOSITION 2007, VOL 8, PTS A AND B
2008: 951-960
View details for Web of Science ID 000254515300105
- Ion Implanted Piezoresistive Cantilever Design and Performance 2008
- Microsystems for biomechanical measurements Pediatr Res 2008; 63 (5): 576-83
- Mechanical Strain Promotes Organization and Contractility of Human Embryonic-Derived Cardiomyocytes in Engineered Myocardial Tissue 2008
- Molecular Imaging of Cardiac Constructs Derived from Human Embryonic Stem Cell 2008
- Artificial dirt: Microfluidic substrates for nematode neurobiology and behavior J Neurophysiol 2008; 99 (6): 3136-43
- Suspension of nanoparticles in SU-8 and characterization of nanocomposite polymers Microelectronics Journal 2008; 39: 228-236
- Modeling and Experimental Validation of Electrostatic Actuation in Aqueous Ionic Media 2008
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Modeling and validation of electrostatic actuation in aqueous ionic media
MEMS 2008: 21ST IEEE INTERNATIONAL CONFERENCE ON MICRO ELECTRO MECHANICAL SYSTEMS, TECHNICAL DIGEST
2008: 467-470
View details for Web of Science ID 000253356900117
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In vivo imaging and evaluation of different biomatrices for improvement of stem cell survival
JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
2007; 1 (6): 465-468
Abstract
Therapeutic effects from injection of stem cells are often hampered by acute donor cell death as well as migration away from damaged areas. This is likely due to the fact that injected cells do not have the physical and biochemical cues for ordered engrafment. Here we evaluate 3 common biomatrices (Matrigel, Collagen I, Purmatrix) that has the potential of providing suitable scaffolds needed to enhance stem cell survival. The longitudinal fate of transplanted stem cells was monitored by reporter imaging techniques.
View details for DOI 10.1002/term.55
View details for Web of Science ID 000256520300008
View details for PubMedID 18163533
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Analysis of nematode mechanics by piezoresistive displacement clamp
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2007; 104 (44): 17376-17381
Abstract
Studying animal mechanics is critical for understanding how signals in the neuromuscular system give rise to behavior and how force-sensing organs and sensory neurons work. Few techniques exist to provide forces and displacements appropriate for such studies. To address this technological gap, we developed a metrology using piezoresistive cantilevers as force-displacement sensors coupled to a feedback system to apply and maintain defined load profiles to micrometer-scale animals. We show that this system can deliver forces between 10(-8) and 10(-3) N across distances of up to 100 mum with a resolution of 12 nN between 0.1 Hz and 100 kHz. We use this new metrology to show that force-displacement curves of wild-type nematodes (Caenorhabditis elegans) are linear. Because nematodes have approximately cylindrical bodies, this finding demonstrates that nematode body mechanics can be modeled as a cylindrical shell under pressure. Little is known about the relative importance of hydrostatic pressure and shell mechanics, however. We show that dissipating pressure by cuticle puncture or decreasing it by hyperosmotic shock has only a modest effect on stiffness, whereas defects in the dpy-5 and lon-2 genes, which alter body shape and cuticle proteins, decrease and increase stiffness by 25% and 50%, respectively. This initial analysis of C. elegans body mechanics suggests that shell mechanics dominates stiffness and is a first step in understanding how body mechanics affect locomotion and force sensing.
View details for DOI 10.1073/pnas.0702138104
View details for Web of Science ID 000250638400028
View details for PubMedID 17962419
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SU-8 MEMS Fabry-Perot pressure sensor
SENSORS AND ACTUATORS A-PHYSICAL
2007; 138 (1): 52-62
View details for DOI 10.1016/j.sna.2007.04.047
View details for Web of Science ID 000248296900008
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Biocompatible coatings for CMUTs in a harsh, aqueous environment
JOURNAL OF MICROMECHANICS AND MICROENGINEERING
2007; 17 (5): 994-1001
View details for DOI 10.1088/0960-1317/17/5/020
View details for Web of Science ID 000246551600022
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Design and characterization of microfabricated piezoresistive floating element-based shear stress sensors
ELSEVIER SCIENCE SA. 2007: 77-87
View details for DOI 10.1016/j.sna.2006.04.035
View details for Web of Science ID 000245066000010
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Transparent SU-8 three-axis micro strain gauge force sensing pillar arrays for biological applications
TRANSDUCERS '07 & EUROSENSORS XXI, DIGEST OF TECHNICAL PAPERS, VOLS 1 AND 2
2007
View details for Web of Science ID 000249603700562
- Characteristics of Parylene Coatings for CMUTs in a Harsh, Aqueous Environment Journal of Micromechanics and Microengineering 2007; 17: 994-1001
- Biological measurements of C. Elegans touch sensitivity with microfabricated force sensors 2007
- Application of a modified quality function deployment method for MEMS 2007
- Characterization of the DRIE Process for ETWI for Piezoresistive Inertial Sensors NNIN REU Research Accomplishments 2007: 88-89
- In vivo imaging and evaluation of different biomatrices for improvement of stem cell survival J Tissue Eng Regen Med. 2007; 1 (6): 465-8
- A Vapor-venting, micromachined heat exchanger for electronics cooling 2007
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Differential electrode design for electrostatic actuator in conducting media
TRANSDUCERS '07 & EUROSENSORS XXI, DIGEST OF TECHNICAL PAPERS, VOLS 1 AND 2
2007
View details for Web of Science ID 000249603700281
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Biomems platform for electromechanical stimulation of cell culture
PROCEEDING OF THE ASME SUMMER BIOENGINEERING CONFERENCE - 2007
2007: 63-64
View details for Web of Science ID 000252105700032
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Pulsatile pressure system for cellular mechanical stimulation
PROCEEDING OF THE ASME SUMMER BIOENGINEERING CONFERENCE - 2007
2007: 1009-1010
View details for Web of Science ID 000252105700505
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Special Issue on Life Science Automation
IEEE TRANSACTIONS ON AUTOMATION SCIENCE AND ENGINEERING
2006; 3 (2): 137-140
View details for DOI 10.1109/TASE.2006.871475
View details for Web of Science ID 000236673600001
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Piezoresistive MEMS underwater shear stress sensors
MEMS 2006: 19TH IEEE INTERNATIONAL CONFERENCE ON MICRO ELECTRO MECHANICAL SYSTEMS, TECHNICAL DIGEST
2006: 626-629
View details for Web of Science ID 000236994500157
- Experimental Characterization of Frequency Dependent Electrostatic Actuator for Aqueous Media 2006
- A Biocompatible Coating for Capactive Micromachined Ultrasonic Transducers 2006
- Development of an Imaging System for On-Line Assessment of Human Embryonic Stem-Cell Derived Cardiomyocytes 2006
- NSF/NASA-GSFC MEMS Education Workshop Outcomes 2006
- Micro and Nano Scale Education at Stanford University 2006
- Mechanical Properties of Wild Type and Mutant Caenorhabditis Elegans using a Closed Loop Piezoresistive Cantilever Indentation System 2006
- Design of BioMEMS device for electromechanical stimulation of hESC 2006
- Design of a Low Noise, Temperature Compensated, Piezoresistive Cantilever 2006
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A microfabricated direct methanol fuel cell with integrated electroosmotic pump
MEMS 2006: 19TH IEEE INTERNATIONAL CONFERENCE ON MICRO ELECTRO MECHANICAL SYSTEMS, TECHNICAL DIGEST
2006: 938-941
View details for Web of Science ID 000236994500235
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Development of an SU-8 Fabry Perot blood pressure sensor
MEMS 2005 MIAMI: TECHNICAL DIGEST
2005: 810-813
View details for Web of Science ID 000228430000201
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Noise studies in implanted piezoresistors
MICRO-ELECTRO-MECHANICAL SYSTEMS - 2005
2005; 7: 87-93
View details for Web of Science ID 000243038100014
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Measurement of mechanical properties of Caenorhabditis elegans with a piezoresistive microcantilever system
2005 3RD IEEE/EMBS SPECIAL TOPIC CONFERENCE ON MICROTECHNOLOGY IN MEDICINE AND BIOLOGY
2005: 400-403
View details for Web of Science ID 000234204800125
- Integration of K-12 Outreach with Design Projects in an Introductory Mechanical Engineering Course 2005
- Noise Studies in Implanted Piezoresistors 2005
- Characterization of modified polymers for high elongation strain sensing 2005
- Measurement of mechanical properties of Caenorhabditis elegans with a piezoresistive microcantilever system 2005
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Design, fabrication, and characterization of piezoresistive MEMS shear stress sensors
MICRO-ELECTRO-MECHANICAL SYSTEMS - 2005
2005; 7: 531-536
View details for Web of Science ID 000243038100083
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Strain transduction in conductor-modified polymers
MICRO- AND NANOSYSTEMS-MATERIALS AND DEVICES
2005; 872: 49-54
View details for Web of Science ID 000234461000008
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Measurement system for low force and small displacement contacts
JOURNAL OF MICROELECTROMECHANICAL SYSTEMS
2004; 13 (2): 220-229
View details for Web of Science ID 000220759300008
- presentation: Piezoresistive MEMS Underwater Shear Stress Sensor 2004
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Fundamental noise in MEMS force sensors
NOISE AND INFORMATION IN NANOELECTRONICS, SENSORS, AND STANDARDS II
2004; 5472: 143-151
View details for DOI 10.1117/12.549814
View details for Web of Science ID 000223225600017
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Piezoresistive cantilevers and measurement system for characterizing low force electrical contacts
SENSORS AND ACTUATORS A-PHYSICAL
2003; 104 (1): 68-77
View details for DOI 10.1016/S0924-4247(02)00485-5
View details for Web of Science ID 000181236100011
- Piezoresistive Cantilevers and Measurement System for Characterizing Low Force Electrical Contacts Sens. Actuators A, Phys., Sensors and Actuators A (Physical) 2003; 104 (1): 68 - 77
- Low Force Contact Resistance Measurements of Thin Film Gold Using Micromachined Piezoresistive Cantilevers 2001
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Low force electrical contact measurements using piezoresistive MEMS cantilevers to characterize thin-film metallization
TRANSDUCERS '01: EUROSENSORS XV, DIGEST OF TECHNICAL PAPERS, VOLS 1 AND 2
2001: 1032-1035
View details for Web of Science ID 000172547800237
- Low force electrical contact measurements using piezoresistive cantilevers to characterize thin-film metallization 2001
- A Three-Axis Micromachined Force Sensor for Studying Cockroach Biomechanics 2000
- Design of piezoresistive cantilevers for low force electrical contact measurements 2000
- Layered Manufacturing with Embedded Components: Process Planning Considerations 1999
- Velocity Measurements in the Flow Around an Rotating End Mill 1998
- Monitoring End Mill Contact Using Acoustic Emission 1996
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IMPROVEMENT OF SYMPTOMS IN TOURETTE SYNDROME BY PIQUINDONE, A NOVEL DOPAMINE-2 RECEPTOR ANTAGONIST
INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY
1986; 1 (3): 216-220
Abstract
We have hypothesized that symptoms of Tourette Syndrome (TS) may represent D2 (dopamine-2) receptor hyperactivity. We treated 4 TS patients with piquindone, a novel D2 receptor antagonist designed via a 3-dimensional model of dopamine receptors. All 4 patients experienced a clinically obvious reduction of tics. Sedation that decreased over time was the only adverse effect. Haloperidol, the current treatment of choice of TS, is limited primarily by its extrapyramidal side-effects. However, piquindone produced therapeutic effects without disabling side-effects. Motor tics responded at lower doses than vocal tics. All patients expressed a strong subjective preference for piquindone over haloperidol. Our results suggest that therapeutic efficacy of a D2 receptor antagonist in TS can be achieved without production of disabling extrapyramidal-side effects. These results also support the proposal that TS may be mediated by hyperactive D2 receptors.
View details for Web of Science ID A1986F845600004
View details for PubMedID 3549873
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CASE-REPORT OF 4 PATIENTS WITH TOURETTE SYNDROME TREATED WITH PIQUINDONE, A D2 RECEPTOR ANTAGONIST
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
1986; 6 (2): 128-130
View details for Web of Science ID A1986A703800022
View details for PubMedID 2871057
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TREATMENT OF TOURETTES SYNDROME WITH RO22-1319, A D-2-RECEPTOR ANTAGONIST
NEW ENGLAND JOURNAL OF MEDICINE
1984; 311 (15): 989-989
View details for Web of Science ID A1984TM02000020
View details for PubMedID 6147753