Probing the Soft Side with Nanoindentation Techniques

Michelle Oyen

Michelle L. Oyen of Cambridge University Engineering Department  will present the talk  “Probing the Soft Side with Nanoindentation Techniques” on Wednesday, March 24 at 3 p.m. in Maryland Hall 110. Dr. Oyen is a lecturer in Mechanics of Biological Materials in the Mechanics and Materials Division and the Engineering for the Life Sciences group at Cambridge University. This seminar is hosted by Professor Tim Weihs and the Johns Hopkins University Department of Materials Science and Engineering. The talk is free and open to all Johns Hopkins faculty, staff and students.

Abstract

The mechanical properties of many “soft” materials are of interest for biomedical applications, including both natural tissues and hydrogels for tissue engineering applications. In the last 15 years, nanoindentation techniques have gained prominence in the mechanical testing community for three reasons: first, the fine resolution in load and displacement transducers, second the fine spatial resolution for mapping local mechanical properties, and finally the relative ease of performing mechanical testing. In the current studies, we extend the scope of nanoindentation testing with commercial indenters to quantitative measurements on kPa materials. Different forms of the material constitutive response were considered with an emphasis on time-dependent viscoelastic or poroelastic deformation. Applications are the considered for hydrated tissues and hydrogels including articular cartilage, bone and mechanically graded hydrogels. Further investigations using adaptations of these nanoindentation techniques examine nano-scale adhesion and mechanical outcomes in stem cell differentiation. This study demonstrates the potential for high-throughput mechanical screening of soft materials and for mapping property gradients in inhomogeneous materials as these approaches can now be extended to materials in the kilopascal elastic modulus range.

Hopkins biomedical engineering doctoral student wins Weintraub Award

Deok-Ho Kim

Deok-Ho Kim, currently a postdoctoral fellow in the department of Biomedical Engineering, was among 13 graduate students from North America chosen to receive the 2010 Harold M. Weintraub Graduate Student Award, sponsored by the Basic Sciences Division of Fred Hutchinson Cancer Research Center in Seattle, Wash. Nominations were solicited internationally and winners were selected on the basis of the quality, originality and significance of their work.

The award, established in 2000, honors the late Harold M. Weintraub, Ph.D., a founding member of the FHC’s Basic Sciences Division, who in 1995 died from brain cancer at age 49. According to a press release from FHC, “Weintraub was an international leader in the field of molecular biology; among his many contributions, he identified genes responsible for instructing cells to differentiate, or develop, into specific tissues such as muscle and bone.”

Kim will receive a certificate, travel expenses and an honorarium from the Weintraub and Groudine Fund, established to foster intellectual exchange through the promotion of programs for graduate students, fellows and visiting scholars. Kim works in the laboratory of Andre Levchenko, associate professor of biomedical engineering at Johns Hopkins University’s Whiting School of Engineering and an affiliated faculty member of the Institute for NanoBioTechnology.

Read more about Kim’s research with Levchenko here.

APL scientist to explain self-assembled artificial cilia from cobalt nanoparticles

Jason Benkoski

Jason Benkoski

Can nanoparticles be used to engineer structures that could be as flexible and useful as the cilia that help bacteria move around?

Jason Benkoski, a senior scientist at Johns Hopkins Applied Physics Laboratory and an affiliated faculty member of Johns Hopkins Institute for NanoBioTechnology, will discuss his current research in this endeavor on March 1  at 1:30 p.m. in the Rome Room, Clark 110 at the Johns Hopkins University Homewood campus. Hosted by the Department of Biomedical Engineering, this talk also will be teleconferenced to the Talbot Library in Traylor 709 at the School of Medicine.

Abstract: Taking inspiration from eukaryotic cilia, we report a method for growing dense arrays of magnetically actuated microscopic filaments. Fabricated from the bottom-up assembly of polymer-coated cobalt nanoparticles, each segmented filament measures approximately 5–15 microns in length and 23.5 nanometers in diameter, which was commensurate with the width of a single nanoparticle. Boasting the flexibility of biological cilia, we envision applications for this technology that include micropumps, micro-flow sensors, microphones with hardware-based voice detection, surfaces with enhanced thermal transfer, switchable, tunable filters, and microscopic locomotion.

Additional Links:

Jason Benkoski’s INBT profile

Johns Hopkins Applied Physics Lab

Drazer wins NSF Career Award

German Drazer

German Drazer (Photo: Will Kirk)

German Drazer, assistant professor in the Department of Chemical and Biomolecular Engineering and affiliated faculty member of Johns Hopkins Institute for NanoBioTechnology was recently named a recipient of the National Science Foundation Faculty Early Career Development (CAREER) awards, given in recognition of a young scientist’s commitment to research and education. Drazer was given the award for “Deterministic and Stochastic Transport of Suspended Particles in Periodic Systems: Fundamentals and Applications in Separation Science.” The grant will support his investigations into the transport phenomena that arise in the motion of suspended particles in spatially periodic systems, and the translation of these phenomena into new principles for the manipulation of suspended particles in fluidic devices.

Read more about the work in the Drazer Lab here.

INBT researchers use LEGO to study what happens inside lab-on-a-chip devices

New Hopkins materials science faculty to explain ‘flash nanoprecipitation’

Margarita Herrera-Alonso

Margarita Herrera-Alonso

Margarita Herrera-Alonso, a new assistant professor in Johns Hopkins Department of Materials Science and Engineering, will present the talk, “Block Copolymer Nanoparticles by Flash Nanoprecipitation: Prodrug Strategies,” on Feb. 3, 2010, at 3 p.m. in Maryland Hall 110. This talk is part of the Materials Science seminar course (EN 510.804), but all Hopkins students, faculty and staff are invited to attend.

Abstract

Colloidal particles are proven effective carriers for therapeutic and imaging agents. Protection of solutes (therapeutic and/or imaging) by encapsulation in colloidal particles enhances their biodistribution and pharmacokinetics, prevents degradation during transport, and allows for triggered/controlled release. Choice of the carrier–dendrimer, micelle, liposome, nanoparticle– is largely determined by its loading efficiency, drug content, and delivery rate. Polymer-based carriers are particularly useful given their chemical, compositional and architectural versatility. We are interested in the formulation of drug-loaded polymer-based nanoparticles. The uniqueness of these nanoparticles relies on the method by which they are produced: Flash Nanoprecipitation. Successful encapsulation of solutes in polymer nanoparticles by Flash Nanoprecipitation depends on establishing rapid micromixing conditions and balancing the kinetics of block copolymer self-assembly and solute precipitation. While Flash Nanoprecipitation is an extremely versatile method for solute encapsulation, the resultant nanoparticles are not exempt from undergoing solvent-mediated interparticle mass transfer. This instability can be attenuated by the use of prodrugs. Specific examples of estradiol prodrugs and their encapsulation in a series of poly(ethylene glycol)-based copolymers will be discussed.

Whiting School of Engineering Department of Materials Science and Engineering

Princeton physicist to discuss physics of cancer cell resistance

Physics professor Robert Austin, right, and graduate ¬student Guillaume Lambert observe prostate cancer cells growing on chips of silicon and silicon-based plastic. (Princeton Office of Communications)

The fact that cancer cells frequently re-emerge after initial therapeutic attempts has dogged the efforts of oncologists to save patients’ lives for decades. According to Princeton physicist, Robert H. Austin, cancer cell resistance is primarily a biological reaction to stress and “one of the great unsolved, and deadly, problems in oncology.”

On Thursday, February 4, Austin will discuss, “The Physics of Cancer,” during a 3 p.m. joint colloquium hosted by Johns Hopkins University departments of Physics and Astronomy and Biophysics in the Schafler auditorium of the Bloomberg Center on the Homewood campus. The talk is free and open to the public.

Austin is principal investigator for Princeton’s Physical Science-Oncology Center and a trans-network partner with Johns Hopkins Engineering in Oncology Center, both of which are National Cancer Institute funded organizations.

Austin will address the general principles of physics, ecology, and biology and why recurrence of resistant cancer cells seems to be a universal phenomenon in cancer. He says that “evolution in small, stressed habitats is key to the rapid and inevitable re-emergence of resistance of cancer cells” (and) “that modern techniques of physical probes, genomics, proteomics and nanotechnology will allow us to analyze the evolutionary path of these emergent resistant cells.”

Related Links

Johns Hopkins Engineering in Oncology Center

Flyer for  Prof. Austin’s colloquium

Physical Sciences in Oncology Centers of the National Cancer Institute

Animator, scientist partner to illustrate cover of Advanced Materials

AM_3_U1resizeThe cover of the January 19, 2010 issue of the journal Advanced Materials features a photo illustration executed by Martin Rietveld, web director and animator at Johns Hopkins Institute for NanoBioTechnology. Rietveld’s work illustrates an article about chemomechanical actuators—grippers that open and close like a hand in response to chemical reactions. The paper is based on the research of lead author, doctoral student Jatinder Randhawa in the laboratory of David Gracias, associate professor of chemical and biomolecular engineering and faculty affiliate of the Institute for Nanobiotechnology. Randhawa conceptualized the illustration of his research for the journal cover.

Says Gracias, “Chemomechanical actuation is intellectually appealing since it is widely observed in nature, but chemomechanical actuation is relatively unexplored in human engineering where the dominant strategy to actuate structures is based on electromechanical actuation (i.e. with electrical signals). Here, microstructures open and close reversibly in response to chemical surface oxidation and reduction without the need for any wires or batteries.”

Related links:

Chemomechanical Actuators: Reversible Actuation of Microstructures by Surface-Chemical Modification of Thin-Film Bilayers. Jatinder S. Randhawa, Michael D. Keung, Pawan Tyagi, David H. Gracias.

Johns Hopkins Institute for NanoBioTechnology Animation Studio

David Gracias INBT Faculty Profile

Environmental, health impacts of engineered nanomaterials theme of INBT’s annual symposium

By 2015, the National Science Foundation reports that the nanotechnology industry could be worth as much as $1 trillion. Nanomaterials have many beneficial applications for industry, medicine and basic scientific research. However, because nanomaterials are just a few atoms in size, they also may pose potential risks for human health and the environment.

Cross-sectional autoradiograms of rodent brains showing (A) control physiological state; and (B) and (C) showing distribution of brain injury from an injected neurotoxicant. Red areas indicate the highest concentrations of a biomarker that identifies brain areas that are damaged by the neurotoxicant. (Guilarte Lab/JHU)

Cross-sectional autoradiograms of rodent brains showing (A) control physiological state; and (B) and (C) showing distribution of brain injury from an injected neurotoxicant. Red areas indicate the highest concentrations of a biomarker that identifies brain areas that are damaged by the neurotoxicant. (Guilarte Lab/JHU)

To increase awareness of Hopkins’ research in this emerging area of investigation, the theme for the fourth annual symposium hosted by Johns Hopkins Institute for NanoBioTechnology (INBT) will be environmental and health impacts of engineered nanomaterials. INBT’s symposium will be held Thursday, April 29, from 8 a.m. to 3 p.m. at the university’s Bloomberg School of Public Health in Baltimore, Md.

Morning talks in Sheldon Hall by eight Hopkins faculty experts will discuss neurotoxicity, exposure assessment, manufacture and characterization of nanomaterials, policy implications and many other topics. In the afternoon, a poster session will be held in Feinstone Hall featuring nanobiotechnology research from across the university’s divisions.

INBT is seeking corporate sponsorships for the symposium. Interested parties should contact Thomas Fekete, INBT’s director of corporate partnerships at tmfeke@jhu.edu or 410-516-8891.

Media inquiries should be directed to Mary Spiro, INBT’s science writer and media relations director, at mspiro@jhu.edu or 410-516-4802.

A call for posters announcement will be made at a later date.

More:

Biodegradable nanoparticles ideal carrier for drug delivery

Johns Hopkins University researchers have created biodegradable nanosized particles that can easily slip through the body’s sticky and viscous mucus secretions to deliver a sustained-release medication cargo. The researchers say that these nanoparticles, which degrade over time into harmless components, could one day carry life-saving drugs to patients suffering from dozens of health conditions, including diseases of the eye, lung, gut or female reproductive tract.

The mucus-penetrating biodegradable nanoparticles were developed by an interdisciplinary team led by Justin Hanes, a professor of chemical and biomolecular engineering in Johns Hopkins’ Whiting School of Engineering*. The team’s work was reported recently in the Proceedings of the National Academy of Sciences. Hanes’ collaborators included cystic fibrosis expert Pamela Zeitlin, a professor of pediatrics at the Johns Hopkins School of Medicine and director of Pediatric Pulmonary Medicine at Johns Hopkins Children’s Center.

Individual biodegradable nanoparticle developed by the Justin Hanes Lab at Johns Hopkins University (shown here at microscale for easier imaging) displaying polymer coating as a red fluorescent glow. Hanes' biodegradable nanoparticles have the ability to penetrate mucus barriers in the body to deliver drugs. (Photo by Jie Fu/JHU)

Individual biodegradable nanoparticle developed by the Justin Hanes Lab at Johns Hopkins University (shown here at microscale for easier imaging) displaying polymer coating as a red fluorescent glow. Hanes’ biodegradable nanoparticles have the ability to penetrate mucus barriers in the body to deliver drugs. (Photo by Jie Fu/JHU)

These nanoparticles, Zeitlin said, could be an ideal means of delivering drugs to people with cystic fibrosis, a disease that kills children and adults by altering the mucus barriers in the lung and gut. “Cystic fibrosis mucus is notoriously thick and sticky and represents a huge barrier to aerosolized drug delivery,” she said. “In our study, the nanoparticles were engineered to travel through cystic fibrosis mucus at a much greater velocity than ever before, thereby improving drug delivery. This work is critically important to moving forward with the next generation of small molecule– and gene-based therapies.”

Beyond their potential applications for cystic fibrosis patients, the nanoparticles also could be used to help treat disorders such as lung and cervical cancer and inflammation of the sinuses, eyes, lungs and gastrointestinal tract, said Benjamin C. Tang, lead author of the journal article and a postdoctoral fellow in the Department of Chemical and Biomolecular Engineering. “Chemotherapy is typically given to the whole body and has many undesired side effects,” he said. “If drugs are encapsulated in these nanoparticles and inhaled directly into the lungs of lung cancer patients, drugs may reach lung tumors more effectively and improved outcomes may be achieved, especially for patients diagnosed with early stage non–small cell lung cancer.”

“If drugs are encapsulated in these nanoparticles and inhaled directly into the lungs of lung cancer patients, drugs may reach lung tumors more effectively and improved outcomes may be achieved, especially for patients diagnosed with early stage non–small cell lung cancer.” ~ Ben Tang

In the lungs, eyes, gastrointestinal tract and other areas, the human body produces layers of mucus to protect sensitive tissue. But an undesirable side effect is that these mucus barriers can also keep helpful medications away.

In proof-of-concept experiments, previous research teams led by Hanes earlier demonstrated that latex particles coated with polyethylene glycol could slip past mucus coatings. But latex particles are not a practical material for delivering medication to human patients because they are not broken down by the body. In the new study, the researchers described how they took an important step forward in making new particles that biodegrade into harmless components while delivering their drug payload over time.

“The major advance here is that we were able to make biodegradable nanoparticles that can rapidly penetrate thick and sticky mucus secretions, and that these particles can transport a wide range of therapeutic molecules, from small molecules such as chemotherapeutics and steroids to macromolecules such as proteins and nucleic acids,” Hanes said. “Previously, we could not get these kinds of sustained-release treatments through the body’s sticky mucus layers effectively.”

The new biodegradable particles comprise two parts made of molecules routinely used in existing medications. An inner core, composed largely of polysebacic acid, or PSA, traps therapeutic agents inside. A particularly dense outer coating of polyethylene glycol, or PEG, molecules, which are linked to PSA, allows a particle to move through mucus nearly as easily as if it were moving through water and also permits the drug to remain in contact with affected tissues for an extended period of time.

In Hanes’ previous studies with mucus-penetrating particles, latex particles could be effectively coated with PEG but could not release drugs or biodegrade. Unlike latex, however, PSA can degrade into naturally occurring molecules that are broken down and flushed away by the body through the kidney, for example. As the particles break down, the drugs loaded inside are released.

This property of PSA enables the sustained release of drugs, said Samuel Lai, assistant research professor in the Department of Chemical and Biomolecular Engineering, while designing them for mucus penetration allows them to more readily reach inaccessible tissues.

Biodegradable nanoparticles produced by the Justin Hanes Lab at Johns Hopkins University visualized under a scanning electron microscope. (Photo by Ben Tang and Mark Koontz/JHU)

Biodegradable nanoparticles produced by the Justin Hanes Lab at Johns Hopkins University visualized under a scanning electron microscope. (Photo by Ben Tang and Mark Koontz/JHU)

Jie Fu, an assistant research professor, also from the Department of Chemical and Biomolecular Engineering, said, “As it degrades, the PSA comes off along with the drug over a controlled amount of time that can reach days to weeks.”

PEG acts as a shield to protect the particles from interacting with proteins in mucus that would cause them to be cleared before releasing their contents. In a related research report, the group showed that the particles can efficiently encapsulate several chemotherapeutics, and that a single dose of drug-loaded particles was able to limit tumor growth in a mouse model of lung cancer for up to 20 days.

Hanes, Zeitlin, Lai and Fu are all affiliated with the Johns Hopkins Institute for NanoBioTechnology. Other authors on the paper are Ying-Ying Wang, Jung Soo Suk and Ming Yang, doctoral students in the Johns Hopkins Department of Biomedical Engineering; Michael P. Boyle, an associate professor in Pulmonary and Critical Care Medicine at the Johns Hopkins School of Medicine; and Michelle Dawson, an assistant professor at the Georgia Institute of Technology.

This work was supported in part by funding from the National Institutes of Health, a National Center for Research Resources Clinical and Translational Science Award, the Cystic Fibrosis Foundation, the National Science Foundation and a Croucher Foundation Fellowship.

The technology described in the journal article is protected by patents managed by the Johns Hopkins Technology Transfer Office and is licensed exclusively by Kala Pharmaceuticals. Justin Hanes is a paid consultant to Kala Pharmaceuticals, a startup company in which he holds equity, and is a member of its board. The terms of these arrangements are being managed by The Johns Hopkins University in accordance with its conflict-of-interest policies.

(*At the time that this research was published, Hanes had his primary affiliation with the Whiting School of Engineering Department of Chemical and Biomolecular Engineering. Hanes’ current primary affiliation is with the Johns Hopkins School of Medicine Department of Ophthalmology.)

Related Links

Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier. PNAS 2009 106:19268-19273; published online before print November 9, 2009.  [Institutional access required.]

Hanes Lab

Johns Hopkins Children’s Center

Institute for NanoBioTechnology

Story by Mary Spiro and Jacob Koskimaki with materials provided by Johns Hopkins Technology Transfer.

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Chemical and biomolecular engineer Denis Wirtz named Smoot professor

Denis Wirtz. Photo by Will Kirk/JHU

Denis Wirtz. Photo by Will Kirk/JHU

Denis Wirtz, Johns Hopkins University professor of chemical and biomolecular engineering and director of the Engineering in Oncology Center, has been named the Theophilus Halley Smoot Professor in the Whiting School of Engineering. University president Ronald J. Daniels and the Board of Trustees determined the recipient.

Wirtz is the founding associate director of the Johns Hopkins Institute for NanoBioTechnology. He was recently named a 2009 fellow of the American Academy for the Advancement of Science in the Engineering Section for his contributions to cell micromechanics, cell adhesion, and for the development and application of particle tracking methods that probe the micromechanical properties of living cells.

He is on the Editorial Boards of Biophysical Journal, Cell Adhesion and Migration and J. Nanomedicine. In 2005, he was named a fellow of the American Institute for Medical and Biological Engineering. Wirtz won the National Science Foundation Career Award in 1996 and the Whitaker Foundation Biomedical Engineering Foundation Award in 1997.

Wirtz came to Johns Hopkins faculty in 1994 and completing a postdoctoral fellowship in Physics and Biophysics at ESPCI (ParisTech). Wirtz earned his PhD in Chemical Engineering from Stanford University in 1993.

An announcement from the Whiting School’s dean Nick Jones stated that, “Throughout his time at Johns Hopkins, Denis has distinguished himself as an outstanding scholar and teacher. Additionally, Denis’ role as a catalyst for interdisciplinary research and collaboration at the university has proven extremely effective, both in terms of the research he conducts and the support he has attracted over the years. I am confident that his current research into the physical basis for cell adhesion and de-adhesion will prove critical to our understanding of the metastasis of cancer and enable important breakthroughs in the diagnosis and treatment of cancer in the years to come.”

The Smoot Professorship was established in 1981 through the estate of Theophilus H. Smoot, who joined Johns Hopkins as a research assistant in the Department of Mechanical Engineering in 1942 and later a research associate in the department in 1946. Upon the passing of Mr. Smoot in 1976 and his widow, Helen A. Smoot in 1980, the Theophilus Halley Smoot Fund for Engineering Science was created.  The first Smoot Professorship was awarded in 1981 to Stanley Corrsin, a professor and former chair in the department of mechanical engineering. Robert E. Green, Jr., professor in the department of materials science, held the professorship from 1988 through 2007.

Presentation of the Smoot professorship will occur in the spring.

Wirtz Lab

Named Professorships of The Johns Hopkins University

Johns Hopkins Institute for NanoBioTechnology

Johns Hopkins Engineering in Oncology Center

Story by Mary Spiro and from materials provided by the Whiting School of Engineering.