Publications by authors named "Elise A Corbin"

17 Publications

  • Page 1 of 1

Simultaneous time-varying viscosity, elasticity, and mass measurements of single adherent cancer cells across cell cycle.

Sci Rep 2020 07 30;10(1):12803. Epub 2020 Jul 30.

Department of Mechanical Science and Engineering, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA.

Biophysical studies on single cells have linked cell mechanics to physiology, functionality and disease. Evaluation of mass and viscoelasticity versus cell cycle can provide further insights into cell cycle progression and the uncontrolled proliferation of cancer. Using our pedestal microelectromechanical systems resonant sensors, we have developed a non-contact interferometric measurement technique that simultaneously tracks the dynamic changes in the viscoelastic moduli and mass of adherent colon (HT-29) and breast cancer (MCF-7) cells from the interphase through mitosis and then to the cytokinesis stages of their growth cycle. We show that by combining three optomechanical parameters in an optical path length equation and a two-degree-of-freedom model, we can simultaneously extract the viscoelasticity and mass as a function of the nano-scaled membrane fluctuation of each adherent cell. Our measurements are able to discern between soft and stiff cells across the cell cycle and demonstrated sharp viscoelastic changes due to cortical stiffening around mitosis. Cell rounding before division can be detected by measurement of mechanical coupling between the cells and the sensors. Our measurement device and method can provide for new insights into the mechanics of single adherent cells versus time.
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http://dx.doi.org/10.1038/s41598-020-69638-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393350PMC
July 2020

Tunable and Reversible Substrate Stiffness Reveals a Dynamic Mechanosensitivity of Cardiomyocytes.

ACS Appl Mater Interfaces 2019 Jun 30;11(23):20603-20614. Epub 2019 May 30.

Department of Physics , Bryn Mawr College , Bryn Mawr , Pennsylvania 19010 , United States.

New directions in material applications have allowed for the fresh insight into the coordination of biophysical cues and regulators. Although the role of the mechanical microenvironment on cell responses and mechanics is often studied, most analyses only consider static environments and behavior, however, cells and tissues are themselves dynamic materials that adapt in myriad ways to alterations in their environment. Here, we introduce an approach, through the addition of magnetic inclusions into a soft poly(dimethylsiloxane) elastomer, to fabricate a substrate that can be stiffened nearly instantaneously in the presence of cells through the use of a magnetic gradient to investigate short-term cellular responses to dynamic stiffening or softening. This substrate allows us to observe time-dependent changes, such as spreading, stress fiber formation, Yes-associated protein translocation, and sarcomere organization. The identification of temporal dynamic changes on a short time scale suggests that this technology can be more broadly applied to study targeted mechanisms of diverse biologic processes, including cell division, differentiation, tissue repair, pathological adaptations, and cell-death pathways. Our method provides a unique in vitro platform for studying the dynamic cell behavior by better mimicking more complex and realistic microenvironments. This platform will be amenable to future studies aimed at elucidating the mechanisms underlying mechanical sensing and signaling that influence cellular behaviors and interactions.
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http://dx.doi.org/10.1021/acsami.9b02446DOI Listing
June 2019

Aligning Synthetic Hippocampal Neural Circuits via Self-Rolled-Up Silicon Nitride Microtube Arrays.

ACS Appl Mater Interfaces 2018 Oct 9;10(42):35705-35714. Epub 2018 Oct 9.

Department of Bioengineering , University of Illinois at Urbana-Champaign , Urbana , Illinois 61801 , United States.

Directing neurons to form predetermined circuits with the intention of treating neurological disorders and neurodegenerative diseases is a fundamental goal and current challenge in neuroengineering. Until recently, only neuronal aggregates were studied and characterized in culture, which can limit information gathered to populations of cells. In this study, we use a substrate constructed of arrays of strain-induced self-rolled-up membrane 3D architectures. This results in changes in the neuronal architecture and altered growth dynamics of neurites. Hippocampal neurons from postnatal rats were cultured at low confluency (∼250 cells mm) on an array of transparent rolled-up microtubes (μ-tubes; 4-5 μm diameter) of varying topographical arrangements. Neurite growth on the μ-tubes was characterized and compared to controls in order to establish a baseline for alignment imposed by the topography. Compared to control substrates, neurites are significantly more aligned toward the 0° reference on the μ-tube array. Pitch (20-60 and 100 μm) and μ-tube length (30-80 μm) of array elements were also varied to investigate their impact on neurite alignment. We found that alignment was improved by the gradient pitch arrangement and with longer μ-tubes. Application of this technology will enhance the ability to construct intentional neural circuits through array design and manipulation of individual neurons and can be adapted to address challenges in neural repair, reinnervation, and neuroregeneration.
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http://dx.doi.org/10.1021/acsami.8b10233DOI Listing
October 2018

Increased Afterload Augments Sunitinib-Induced Cardiotoxicity in an Engineered Cardiac Microtissue Model.

JACC Basic Transl Sci 2018 Apr 30;3(2):265-276. Epub 2018 May 30.

Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Sunitinib, a multitargeted oral tyrosine kinase inhibitor, used widely to treat solid tumors, results in hypertension in up to 47% and left ventricular dysfunction in up to 19% of treated individuals. The relative contribution of afterload toward inducing cardiac dysfunction with sunitinib treatment remains unknown. We created a preclinical model of sunitinib cardiotoxicity using engineered microtissues that exhibited cardiomyocyte death, decreases in force generation, and spontaneous beating at clinically relevant doses. Simulated increases in afterload augmented sunitinib cardiotoxicity in both rat and human microtissues, which suggest that antihypertensive therapy may be a strategy to prevent left ventricular dysfunction in patients treated with sunitinib.
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http://dx.doi.org/10.1016/j.jacbts.2017.12.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059907PMC
April 2018

Optomechanical microrheology of single adherent cancer cells.

APL Bioeng 2018 Mar 5;2(1):016108. Epub 2018 Mar 5.

Department of Mechanical Science and Engineering, University of Illinois Urbana-Champaign, Urbana, Illinois 61801, USA.

There is a close relationship between the mechanical properties of cells and their physiological function. Non-invasive measurements of the physical properties of cells, especially of adherent cells, are challenging to perform. Through a non-contact optical interferometric technique, we measure and combine the phase, amplitude, and frequency of vibrating silicon pedestal micromechanical resonant sensors to quantify the "loss tangent" of individual adherent human colon cancer cells (HT-29). The loss tangent, a dimensionless ratio of viscoelastic energy loss and energy storage - a measure of the viscoelasticity of soft materials, obtained through an optical path length model, was found to be 1.88   0.08 for live cells and 4.32   0.13 for fixed cells, revealing significant changes (p < 0.001) in mechanical properties associated with estimated nanoscale cell membrane fluctuations of 3.86   0.2 nm for live cells and 2.87   0.1 nm for fixed cells. By combining these values with the corresponding two-degree-of-freedom Kelvin-Voigt model, we obtain the elastic stiffness and viscous loss associated with each individual cell rather than estimations from a population. The technique is unique as it decouples the heterogeneity of individual cells in our population and further refines the viscoelastic solution space.
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http://dx.doi.org/10.1063/1.5010721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481704PMC
March 2018

Mechanically dynamic PDMS substrates to investigate changing cell environments.

Biomaterials 2017 Nov 17;145:23-32. Epub 2017 Aug 17.

Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:

Mechanics of the extracellular matrix (ECM) play a pivotal role in governing cell behavior, such as cell spreading and differentiation. ECM mechanics have been recapitulated primarily in elastic hydrogels, including with dynamic properties to mimic complex behaviors (e.g., fibrosis); however, these dynamic hydrogels fail to introduce the viscoelastic nature of many tissues. Here, we developed a two-step crosslinking strategy to first form (via platinum-catalyzed crosslinking) networks of polydimethylsiloxane (PDMS) and then to increase PDMS crosslinking (via thiol-ene click reaction) in a temporally-controlled manner. This photoinitiated reaction increased the compressive modulus of PDMS up to 10-fold within minutes and was conducted under cytocompatible conditions. With stiffening, cells displayed increased spreading, changing from ∼1300 to 1900 μm and from ∼2700 to 4600 μm for fibroblasts and mesenchymal stem cells, respectively. In addition, higher myofibroblast activation (from ∼2 to 20%) for cardiac fibroblasts was observed with increasing PDMS substrate stiffness. These results indicate a cellular response to changes in PDMS substrate mechanics, along with a demonstration of a mechanically dynamic and photoresponsive PDMS substrate platform to model the dynamic behavior of ECM.
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http://dx.doi.org/10.1016/j.biomaterials.2017.08.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871432PMC
November 2017

Evidence of differential mass change rates between human breast cancer cell lines in culture.

Biomed Microdevices 2017 03;19(1):10

Micro and Nanotechnology Laboratory, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA.

Investigating the growth signatures of single cells will determine how cell growth is regulated and cell size is maintained. The ability to precisely measure such changes and alterations in cell size and cell mass could be important for applications in cancer and drug screening. Here, we measure the mass growth rate of individual benign (MCF-10A), non-invasive (MCF-7), and highly-invasive malignant (MDA-MB-231) breast cancer cells. A micro-patterning technique was employed to allow for the long-term growth of motile cells. Results show mass growth rates at 4.8%, 1.2%, and 2.8% for MCF-10A, MCF-7, and MDA-MB-231, demonstrating that normal cells have a higher mass growth rate than cancerous cells. All the cell lines show an increase in mass change rate indicating that the mass accumulation rate is exponential over a single cell cycle. The growth rates measured with our MEMS sensor are compared with doubling times obtained through conventional bulk analysis techniques, and exhibit excellent agreement.
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http://dx.doi.org/10.1007/s10544-017-0151-xDOI Listing
March 2017

Optomechanical measurement of the stiffness of single adherent cells.

Lab Chip 2015 Sep 29;15(17):3460-4. Epub 2015 Jul 29.

Division of Electrical and Computer Engineering, Louisiana State University, Baton Rouge, LA 70803, USA.

Recent advances in mechanobiology have accumulated strong evidence showing close correlations between the physiological conditions and mechanical properties of cells. In this paper, a novel optomechanical technique to characterize the stiffness of single adherent cells attached on a substrate is reported. The oscillation in a cell's height on a vertically vibrating reflective substrate is measured with a laser Doppler vibrometer as apparent changes in the phase of the measured velocity. This apparent phase shift and the height oscillation are shown to be affected by the mechanical properties of human colorectal adenocarcinoma cells (HT-29). The reported optomechanical technique can provide high-throughput stiffness measurement of single adherent cells over time with minimal perturbation.
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http://dx.doi.org/10.1039/c5lc00444fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841955PMC
September 2015

Slowing DNA Transport Using Graphene-DNA Interactions.

Adv Funct Mater 2015 Feb;25(6):936-946

Micro and Nanotechnology Laboratory, 208 North Wright Street Urbana, IL 61801, USA. Department of Electrical and Computer Engineering, University of Illinois Urbana-Champaign Urbana, IL 61801, USA. Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.

Slowing down DNA translocation speed in a nanopore is essential to ensuring reliable resolution of individual bases. Thin membrane materials enhance spatial resolution but simultaneously reduce the temporal resolution as the molecules translocate far too quickly. In this study, the effect of exposed graphene layers on the transport dynamics of both single (ssDNA) and double-stranded DNA (dsDNA) through nanopores is examined. Nanopore devices with various combinations of graphene and AlO dielectric layers in stacked membrane structures are fabricated. Slow translocations of ssDNA in nanopores drilled in membranes with layers of graphene are reported. The increased hydrophobic interactions between the ssDNA and the graphene layers could explain this phenomenon. Further confirmation of the hydrophobic origins of these interactions is obtained through reporting significantly faster translocations of dsDNA through these graphene layered membranes. Molecular dynamics simulations confirm the preferential interactions of DNA with the graphene layers as compared to the dielectric layer verifying the experimental findings. Based on our findings, we propose that the integration of multiple stacked graphene layers could slow down DNA enough to enable the identification of nucleobases.
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http://dx.doi.org/10.1002/adfm.201403719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497588PMC
February 2015

Biophysical properties of human breast cancer cells measured using silicon MEMS resonators and atomic force microscopy.

Lab Chip 2015 Feb;15(3):839-47

Department of Mechanical Science and Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.

Biophysical studies on individual cells can help to establish the relationship between mechanics and biological function. In the case of cancer, mechanical properties of cells have been linked to metastatic activity and disease progression and can be crucial for understanding cellular physiology and metabolism. In this study, we report measurements of the stiffness of breast cancer cells using a novel silicon MEMS resonant sensor and validated the results with atomic force microscopy (AFM). We measured the mass and stiffness of individual benign (MCF-10A), non-invasive malignant (MCF-7), and highly-invasive malignant (MDA-MB-231) breast cancer cells using the silicon resonant MEMS sensors. The sensor extracts the average stiffness value of the whole cell and allows comparison of stiffness of different cell types. We found differences between the cell lines in both elasticity and viscosity, and confirmed our observations through independent measurements with atomic force microscopy (AFM). Coupled with measurements over time, this approach could lead to a multimodal investigation of both growth and physical properties of single cells. The mechanical property sensitivity and resolution of these pedestal sensors were investigated to understand the significance of the frequency shift during operation. The lowest achievable spring constant and damping constant resolutions have a range of 0.06 to 17.10 mN m(-1) and 1.63 to 1.96 nN s m(-1), respectively, measured across the range of physiological cell mechanical properties.
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http://dx.doi.org/10.1039/c4lc01179aDOI Listing
February 2015

Measuring physical properties of neuronal and glial cells with resonant microsensors.

Anal Chem 2014 May 30;86(10):4864-72. Epub 2014 Apr 30.

Department of Mechanical Engineering, University of Illinois Urbana-Champaign , Urbana, Illinois 61801, United States.

Microelectromechanical systems (MEMS) resonant sensors provide a high degree of accuracy for measuring the physical properties of chemical and biological samples. These sensors enable the investigation of cellular mass and growth, though previous sensor designs have been limited to the study of homogeneous cell populations. Population heterogeneity, as is generally encountered in primary cultures, reduces measurement yield and limits the efficacy of sensor mass measurements. This paper presents a MEMS resonant pedestal sensor array fabricated over through-wafer pores compatible with vertical flow fields to increase measurement versatility (e.g., fluidic manipulation and throughput) and allow for the measurement of heterogeneous cell populations. Overall, the improved sensor increases capture by 100% at a flow rate of 2 μL/min, as characterized through microbead experiments, while maintaining measurement accuracy. Cell mass measurements of primary mouse hippocampal neurons in vitro, in the range of 0.1-0.9 ng, demonstrate the ability to investigate neuronal mass and changes in mass over time. Using an independent measurement of cell volume, we find cell density to be approximately 1.15 g/mL.
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http://dx.doi.org/10.1021/ac5000625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033632PMC
May 2014

Dissolution chemistry and biocompatibility of single-crystalline silicon nanomembranes and associated materials for transient electronics.

ACS Nano 2014 Jun 9;8(6):5843-51. Epub 2014 Apr 9.

Department of Materials Science and Engineering, Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.

Single-crystalline silicon nanomembranes (Si NMs) represent a critically important class of material for high-performance forms of electronics that are capable of complete, controlled dissolution when immersed in water and/or biofluids, sometimes referred to as a type of "transient" electronics. The results reported here include the kinetics of hydrolysis of Si NMs in biofluids and various aqueous solutions through a range of relevant pH values, ionic concentrations and temperatures, and dependence on dopant types and concentrations. In vitro and in vivo investigations of Si NMs and other transient electronic materials demonstrate biocompatibility and bioresorption, thereby suggesting potential for envisioned applications in active, biodegradable electronic implants.
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http://dx.doi.org/10.1021/nn500847gDOI Listing
June 2014

Micro-patterning of mammalian cells on suspended MEMS resonant sensors for long-term growth measurements.

Lab Chip 2014 Apr;14(8):1401-4

Department of Mechanical Science and Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.

MEMS resonant mass sensors can measure the mass of individual cells, though long-term growth measurements are limited by the movement of cells off the sensor area. Micro-patterning techniques are a powerful approach to control the placement of individual cells in an arrayed format. In this work we present a method for micro-patterning cells on fully suspended resonant sensors through select functionalization and passivation of the chip surface. This method combines high-resolution photolithography with a blanket transfer technique for applying photoresist to avoid damaging the sensors. Cells are constrained to the patterned collagen area on the sensor by pluronic acting as a cell adhesion blocker. This micro-patterning method enables long-term growth measurements, which is demonstrated by a measurement of the change in mass of a human breast cancer cell over 18 h.
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http://dx.doi.org/10.1039/c3lc51217gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4024477PMC
April 2014

Micromechanical properties of hydrogels measured with MEMS resonant sensors.

Biomed Microdevices 2013 Apr;15(2):311-9

Department of Mechanical Science and Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.

Hydrogels have gained wide usage in a range of biomedical applications because of their biocompatibility and the ability to finely tune their properties, including viscoelasticity. The use of hydrogels on the microscale is increasingly important for the development of drug delivery techniques and cellular microenvironments, though the ability to accurately characterize their micromechanical properties is limited. Here we demonstrate the use of microelectromechanical systems (MEMS) resonant sensors to estimate the properties of poly(ethylene glycol) diacrylate (PEGDA) microstructures over a range of concentrations. These microstructures are integrated on the sensors by deposition using electrohydrodynamic jet printing. Estimated properties agree well with independent measurements made using indentation with atomic force microscopy.
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http://dx.doi.org/10.1007/s10544-012-9730-zDOI Listing
April 2013

Characterization of mass and swelling of hydrogel microstructures using MEMS resonant mass sensor arrays.

Small 2012 Aug 11;8(16):2555-62. Epub 2012 Jun 11.

Department of Electrical and Computer Engineering, Micro and Nanotechnology Laboratory, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.

The use of hydrogels for biomedical engineering, and for the development of biologically inspired cellular systems at the microscale, is advancing at a rapid pace. Microelectromechanical system (MEMS) resonant mass sensors enable the mass measurement of a range of materials. The integration of hydrogels onto MEMS resonant mass sensors is demonstrated, and these sensors are used to characterize the hydrogel mass and swelling characteristics. The mass values obtained from resonant frequency measurements of poly(ethylene glycol)diacrylate (PEGDA) microstructures match well with the values independently verified through volume measurements. The sensors are also used to measure the influence of fluids of similar and greater density on the mass measurements of microstructures. The data show a size-dependent increase in gel mass when fluid density is increased. Lastly, volume comparisons of bulk hydrogels with a range polymer concentration (5% to 100% (v/v)) show a non-linear swelling trend.
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http://dx.doi.org/10.1002/smll.201200470DOI Listing
August 2012

Self-heating in piezoresistive cantilevers.

Appl Phys Lett 2011 May 31;98(22):223103. Epub 2011 May 31.

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.
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http://dx.doi.org/10.1063/1.3595485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3129336PMC
May 2011

A microcantilever heater-thermometer with a thermal isolation layer for making thermal nanotopography measurements.

Nanotechnology 2010 Feb 21;21(5):055503. Epub 2009 Dec 21.

Department of Mechanical Science and Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.

This paper presents a microcantilever having a microscale heater-thermometer fabricated from doped single crystal silicon that is mounted on a silicon nitride thermal isolation structure. The silicon nitride isolation structure is in turn connected to doped single crystal silicon legs. The cantilever fabrication, its characterization, and its application in thermal nanotopography measurements are presented in this work. The cantilever can reach temperatures over 600 degrees C with a heating power of 4 mW. The cantilever has a thermal resistance that exceeds 10(5) K W(-1) when away from a substrate. Making a contact-mode scan over a silicon calibration grating of height 20 nm, the cantilever has a topography reading sensitivity of 1.3 x 10(-4) nm(-1), and a topography reading resolution of about 7 pm Hz(-1/2). These performance characteristics compare extremely well to published ones for other kinds of cantilevers.
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http://dx.doi.org/10.1088/0957-4484/21/5/055503DOI Listing
February 2010
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