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Cancer 052716 nanoparticles-nanomedicineHacking metastasis: Nanotechnology researchers find new way to target tumors

 

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Genesis Nanotechnology, Inc. ~ “Great Things from Small Things”

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MSU Fibers 032516 160324104809_1_540x360A microbial protein fiber discovered by a MSU’s Gemma Reguera transports charges at rates high enough to be applied in manmade nanotechnologies.
Credit: Kurt Stepnitz

“This microbial nanowire is made of but a single peptide subunit,” said Gemma Reguera, lead author and MSU microbiologist. “Being made of protein, these organic nanowires are biodegradable and biocompatible. This discovery thus opens many applications in nanoelectronics such as the development of medical sensors and electronic devices that can be interfaced with human tissues.”

Since existing nanotechnologies incorporate exotic metals into their designs, the cost of organic nanowires is much more cost effective as well, she added.

How the nanowires function in nature is comparable to breathing. Bacterial cells, like humans, have to breathe. The process of respiration involves moving electrons out of an organism. Geobacter bacteria use the protein nanowires to bind and breathe metal-containing minerals such as iron oxides and soluble toxic metals such as uranium. The toxins are mineralized on the nanowires’ surface, preventing the metals from permeating the cell.

Reguera’s team purified their protein fibers, which are about 2 nanometers in diameter. Using the same toolset of nanotechnologists, the scientists were able to measure the high velocities at which the proteins were passing electrons.

“They are like power lines at the nanoscale,” Reguera said. “This also is the first study to show the ability of electrons to travel such long distances — more than a 1,000 times what’s been previously proven — along proteins.”

The researchers also identified metal traps on the surface of the protein nanowires that bind uranium with great affinity and could potentially trap other metals. These findings could provide the basis for systems that integrate protein nanowires to mine gold and other precious metals, scrubbers that can be deployed to immobilize uranium at remediation sites and more.

Reguera’s nanowires also can be modified to seek out other materials in which to help them breathe.

“The Geobacter cells are making these protein fibers naturally to breathe certain metals. We can use genetic engineering to tune the electronic and biochemical properties of the nanowires and enable new functionalities. We also can mimic the natural manufacturing process in the lab to mass-produce them in inexpensive and environmentally friendly processes,” Reguera said. “This contrasts dramatically with the manufacturing of humanmade inorganic nanowires, which involve high temperatures, toxic solvents, vacuums and specialized equipment.”

This discovery came from truly listening to bacteria, Reguera said.

“The protein is getting the credit, but we can’t forget to thank the bacteria that invented this,” she said. “It’s always wise to go back and ask bacteria what else they can teach us. In a way, we are eavesdropping on microbial conversations. It’s like listening to our elders, learning from their wisdom and taking it further.”


Story Source:

The above post is reprinted from materials provided by Michigan State University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Sanela Lampa-Pastirk, Joshua P. Veazey, Kathleen A. Walsh, Gustavo T. Feliciano, Rebecca J. Steidl, Stuart H. Tessmer, Gemma Reguera. Thermally activated charge transport in microbial protein nanowires. Scientific Reports, 2016; 6: 23517 DOI: 10.1038/srep23517
Cancer shapeshiftin
Professor Warren Chan (IBBME, ChemE, MSE) has spent the last decade figuring out how to deliver chemotherapy drugs into tumours — and nowhere else. Now his lab has designed a set of nanoparticles attached to strands of DNA that can change …more

Chemotherapy isn’t supposed to make your hair fall out—it’s supposed to kill cancer cells. A new molecular delivery system created at U of T could help ensure that chemotherapy drugs get to their target while minimizing collateral damage.

Many target fast-growing cells. Injected into a patient, they swirl around in the bloodstream acting on fast-growing cells wherever they find them. That includes tumours, but unfortunately also hair follicles, the lining of your digestive system, and your skin.

Professor Warren Chan (IBBME, ChemE, MSE) has spent the last decade figuring out how to deliver into tumours—and nowhere else. Now his lab has designed a set of nanoparticles attached to strands of DNA that can change shape to gain access to diseased tissue.

“Your body is basically a series of compartments,” says Chan. “Think of it as a giant house with rooms inside. We’re trying to figure out how to get something that’s outside, into one specific room. One has to develop a map and a system that can move through the house where each path to the final room may have different restrictions such as height and width.”

One thing we know about : no two tumours are identical. Early-stage breast cancer, for example, may react differently to a given treatment than pancreatic cancer, or even breast cancer at a more advanced stage. Which particles can get inside which tumours depends on multiple factors such as the particle’s size, shape and surface chemistry.

Chan and his research group have studied how these factors dictate the delivery of small molecules and nanotechnologies to tumours, and have now designed a targeted molecular delivery system that uses modular nanoparticles whose shape, size and chemistry can be altered by the presence of specific DNA sequences.

“We’re making shape-changing nanoparticles,” says Chan. “They’re a series of building blocks, kind of like a LEGO set.” The component pieces can be built into many shapes, with binding sites exposed or hidden. They are designed to respond to biological molecules by changing shape, like a key fitting into a lock.

These shape-shifters are made of minuscule chunks of metal with strands of DNA attached to them. Chan envisions that the nanoparticles will float around harmlessly in the blood stream, until a DNA strand binds to a sequence of DNA known to be a marker for cancer. When this happens, the particle changes shape, then carries out its function: it can target the , expose a drug molecule to the cancerous cell, tag the cancerous cells with a signal molecule, or whatever task Chan’s team has designed the nanoparticle to carry out.

Their work was published this week in two key studies in the Proceedings of the National Academy of Sciences and the leading journal Science.

“We were inspired by the ability of proteins to alter their conformation—they somehow figure out how to alleviate all these delivery issues inside the body,” says Chan. “Using this idea, we thought, ‘Can we engineer a nanoparticle to function like a protein, but one that can be programmed outside the body with medical capabilities?'”

Applying nanotechnology and materials science to medicine, and particularly to targeted drug delivery, is still a relatively new concept, but one Chan sees as full of promise. The real problem is how to deliver enough of the nanoparticles directly to the cancer to produce an effective treatment.

“Here’s how we look at these problems: it’s like you’re going to Vancouver from Toronto, but no one tells you how to get there, no one gives you a map, or a plane ticket, or a car—that’s where we are in this field,” he says. “The idea of targeting drugs to tumours is like figuring out how to go to Vancouver. It’s a simple concept, but to get there isn’t simple if not enough information is provided.”

“We’ve only scratched the surface of how nanotechnology ‘delivery’ works in the body, so now we’re continuing to explore different details of why and how tumours and other organs allow or block certain things from getting in,” adds Chan.

He and his group plan to apply the they’ve designed toward personalized nanomedicine—further tailoring their particles to deliver drugs to your precise type of, and nowhere else.

Explore further: Cylindrical nanoparticles more deadly to breast cancer

More information: Edward A. Sykes et al. Tailoring nanoparticle designs to target cancer based on tumor pathophysiology, Proceedings of the National Academy of Sciences(2016). DOI: 10.1073/pnas.1521265113

Cancer Nanoparticle Targets 160210165715_1_540x360In one of the first efforts to date to apply nanotechnology to targeted cancer therapeutics, researchers have created a nanoparticle formulation of a cancer drug that is both effective and nontoxic — qualities harder to achieve with the free drug. Their nanoparticle creation releases the potent but toxic targeted cancer drug directly to tumors, while sparing healthy tissue.

The findings in rodents with human tumors have helped launch clinical trials of the nanoparticle-encapsulated version of the drug, which are currently underway. Aurora kinase inhibitors are molecularly targeted agents that disrupt cancer’s cell cycle.

While effective, the inhibitors have proven highly toxic to patients and have stalled in late-stage trials. Development of several other targeted cancer drugs has been abandoned because of unacceptable toxicity. To improve drug safety and efficacy, Susan Ashton and colleagues designed polymeric nanoparticles called Accurins to deliver an Aurora kinase B inhibitor currently in clinical trials.

The nanoparticle formulation used ion pairing to efficiently encapsulate and control the release of the drug. In colorectal tumor-bearing rats and mice with diffuse large B cell lymphoma, the nanoparticles accumulated specifically in tumors, where they slowly released the drug to cancer cells. Compared to the free drug, the nanoparticle-encapsulated inhibitor blocked tumor growth more effectively at one half the drug dose and caused fewer side effects in the rodents.

Cancer Nanoparticle Targets 160210165715_1_540x360

The polymeric nanoparticle Accurin encapsulates the clinical candidate AZD2811, an Aurora B kinase inhibitor. This material relates to a paper that appeared in the Feb. 10, 2016 issue of Science Translational Medicine, published by AAAS. The paper, by S. Ashton at institution in location, and colleagues was titled, “Aurora kinase inhibitor nanoparticles target tumors with favorable therapeutic index in vivo.”
Credit: Ashton et al., Science Translational Medicine (2016)

A related Focus by David Bearss offers more insights on how Accurin nanoparticles may help enhance the safety and antitumor activity of Aurora kinase inhibitors and other molecularly targeted drugs.


Story Source:

The above post is reprinted from materials provided by American Association for the Advancement of Science. Note: Materials may be edited for content and length.


Journal Reference:

  1. Susan Ashton, Young Ho Song, Jim Nolan, Elaine Cadogan, Jim Murray, Rajesh Odedra, John Foster, Peter A. Hall, Susan Low, Paula Taylor, Rebecca Ellston, Urszula M. Polanska, Joanne Wilson, Colin Howes, Aaron Smith, Richard J. A. Goodwin, John G. Swales, Nicole Strittmatter, Zoltán Takáts, Anna Nilsson, Per Andren, Dawn Trueman, Mike Walker, Corinne L. Reimer, Greg Troiano, Donald Parsons, David De Witt, Marianne Ashford, Jeff Hrkach, Stephen Zale, Philip J. Jewsbury, and Simon T. Barry. Aurora kinase inhibitor nanoparticles target tumors with favorable therapeutic index in vivo. Science Translational Medicine, 2016 DOI: 10.1126/scitranslmed.aad2355

Targeted Drug Delivery 150916162906_1_540x360Nanoparticles disguised as human platelets could greatly enhance the healing power of drug treatments for cardiovascular disease and systemic bacterial infections. These platelet-mimicking nanoparticles, developed by engineers at the University of California, San Diego, are capable of delivering drugs to targeted sites in the body — particularly injured blood vessels, as well as organs infected by harmful bacteria. Engineers demonstrated that by delivering the drugs just to the areas where the drugs were needed, these platelet copycats greatly increased the therapeutic effects of drugs that were administered to diseased rats and mice.

The research, led by nanoengineers at the UC San Diego Jacobs School of Engineering, was published online Sept. 16 in Nature.

“This work addresses a major challenge in the field of nanomedicine: targeted drug delivery with nanoparticles,” said Liangfang Zhang, a nanoengineering professor at UC San Diego and the senior author of the study. “Because of their targeting ability, platelet-mimicking nanoparticles can directly provide a much higher dose of medication specifically to diseased areas without saturating the entire body with drugs.”

Targeted Drug Delivery 150916162906_1_540x360

Pseudocolored scanning electron microscope images of platelet-membrane-coated nanoparticles (orange) binding to the lining of a damaged artery (left) and to MRSA bacteria (right). Each nanoparticle is approximately 100 nanometers in diameter, which is one thousand times thinner than an average sheet of paper.
Credit: Zhang Research Group, UC San Diego Jacobs School of Engineering.

The study is an excellent example of using engineering principles and technology to achieve “precision medicine,” said Shu Chien, a professor of bioengineering and medicine, director of the Institute of Engineering in Medicine at UC San Diego, and a corresponding author on the study. “While this proof of principle study demonstrates specific delivery of therapeutic agents to treat cardiovascular disease and bacterial infections, it also has broad implications for targeted therapy for other diseases such as cancer and neurological disorders,” said Chien.

The ins and outs of the platelet copycats

On the outside, platelet-mimicking nanoparticles are cloaked with human platelet membranes, which enable the nanoparticles to circulate throughout the bloodstream without being attacked by the immune system. The platelet membrane coating has another beneficial feature: it preferentially binds to damaged blood vessels and certain pathogens such as MRSA bacteria, allowing the nanoparticles to deliver and release their drug payloads specifically to these sites in the body.

Enclosed within the platelet membranes are nanoparticle cores made of a biodegradable polymer that can be safely metabolized by the body. The nanoparticles can be packed with many small drug molecules that diffuse out of the polymer core and through the platelet membrane onto their targets.

To make the platelet-membrane-coated nanoparticles, engineers first separated platelets from whole blood samples using a centrifuge. The platelets were then processed to isolate the platelet membranes from the platelet cells. Next, the platelet membranes were broken up into much smaller pieces and fused to the surface of nanoparticle cores. The resulting platelet-membrane-coated nanoparticles are approximately 100 nanometers in diameter, which is one thousand times thinner than an average sheet of paper.

This cloaking technology is based on the strategy that Zhang’s research group had developed to cloak nanoparticles in red blood cell membranes. The researchers previously demonstrated that nanoparticles disguised as red blood cells are capable of removing dangerous pore-forming toxins produced by MRSA, poisonous snake bites and bee stings from the bloodstream.

By using the body’s own platelet membranes, the researchers were able to produce platelet mimics that contain the complete set of surface receptors, antigens and proteins naturally present on platelet membranes. This is unlike other efforts, which synthesize platelet mimics that replicate one or two surface proteins of the platelet membrane.

“Our technique takes advantage of the unique natural properties of human platelet membranes, which have a natural preference to bind to certain tissues and organisms in the body,” said Zhang. This targeting ability, which red blood cell membranes do not have, makes platelet membranes extremely useful for targeted drug delivery, researchers said.

Platelet copycats at work

In one part of this study, researchers packed platelet-mimicking nanoparticles with docetaxel, a drug used to prevent scar tissue formation in the lining of damaged blood vessels, and administered them to rats afflicted with injured arteries. Researchers observed that the docetaxel-containing nanoparticles selectively collected onto the damaged sites of arteries and healed them.

When packed with a small dose of antibiotics, platelet-mimicking nanoparticles can also greatly minimize bacterial infections that have entered the bloodstream and spread to various organs in the body. Researchers injected nanoparticles containing just one-sixth the clinical dose of the antibiotic vancomycin into one of group of mice systemically infected with MRSA bacteria. The organs of these mice ended up with bacterial counts up to one thousand times lower than mice treated with the clinical dose of vancomycin alone.

“Our platelet-mimicking nanoparticles can increase the therapeutic efficacy of antibiotics because they can focus treatment on the bacteria locally without spreading drugs to healthy tissues and organs throughout the rest of the body,” said Zhang. “We hope to develop platelet-mimicking nanoparticles into new treatments for systemic bacterial infections and cardiovascular disease.”


Story Source:

The above post is reprinted from materials provided by University of California – San Diego. The original item was written by Liezel Labios. Note: Materials may be edited for content and length.


Journal Reference:

  1. Che-Ming J. Hu, Ronnie H. Fang, Kuei-Chun Wang, Brian T. Luk, Soracha Thamphiwatana, Diana Dehaini, Phu Nguyen, Pavimol Angsantikul, Cindy H. Wen, Ashley V. Kroll, Cody Carpenter, Manikantan Ramesh, Vivian Qu, Sherrina H. Patel, Jie Zhu, William Shi, Florence M. Hofman, Thomas C. Chen, Weiwei Gao, Kang Zhang, Shu Chien, Liangfang Zhang. Nanoparticle biointerfacing by platelet membrane cloaking. Nature, 2015; DOI: 10.1038/nature15373
 

Elastic NP 150723181609_1_540x360

An international research team based at The University of Texas at Dallas has made electrically conducting fibers that can be reversibly stretched to over 14 times their initial length and whose electrical conductivity increases 200-fold when stretched.

The research team is using the new fibers to make artificial muscles, as well as capacitors whose energy storage capacity increases about tenfold when the fibers are stretched. Fibers and cables derived from the invention might one day be used as interconnects for super-elastic electronic circuits; robots and exoskeletons having great reach; morphing aircraft; giant-range strain sensors; failure-free pacemaker leads; and super-stretchy charger cords for electronic devices.

In a study published in the July 24 issue of the journal Science, the scientists describe how they constructed the fibers by wrapping lighter-than-air, electrically conductive sheets of tiny carbon nanotubes to form a jelly-roll-like sheath around a long rubber core.

The new fibers differ from conventional materials in several ways. For example, when conventional fibers are stretched, the resulting increase in length and decrease in cross-sectional area restricts the flow of electrons through the material. But even a “giant” stretch of the new conducting sheath-core fibers causes little change in their electrical resistance, said Dr. Ray Baughman, senior author of the paper and director of the Alan G. MacDiarmid NanoTech Institute at UT Dallas.

One key to the performance of the new conducting elastic fibers is the introduction of buckling into the carbon nanotube sheets. Because the rubber core is stretched along its length as the sheets are being wrapped around it, when the wrapped rubber relaxes, the carbon nanofibers form a complex buckled structure, which allows for repeated stretching of the fiber.

“Think of the buckling that occurs when an accordion is compressed, which makes the inelastic material of the accordion stretchable,” said Baughman, the Robert A. Welch Distinguished Chair in Chemistry at UT Dallas.

“We make the inelastic carbon nanotube sheaths of our sheath-core fibers super stretchable by modulating large buckles with small buckles, so that the elongation of both buckle types can contribute to elasticity. These amazing fibers maintain the same electrical resistance, even when stretched by giant amounts, because electrons can travel over such a hierarchically buckled sheath as easily as they can traverse a straight sheath.”

Dr. Zunfeng Liu, lead author of the study and a research associate in the NanoTech Institute, said the structure of the sheath-core fibers “has further interesting and important complexity.” Buckles form not only along the fiber’s length, but also around its circumference.

“Shrinking the fiber’s circumference during fiber stretch causes this second type of reversible hierarchical buckling around its circumference, even as the buckling in the fiber direction temporarily disappears,” Liu said. “This novel combination of buckling in two dimensions avoids misalignment of nanotube and rubber core directions, enabling the electrical resistance of the sheath-core fiber to be insensitive to stretch.”

By adding a thin overcoat of rubber to the sheath-core fibers and then another carbon nanotube sheath, the researchers made strain sensors and artificial muscles in which the buckled nanotube sheaths serve as electrodes and the thin rubber layer is a dielectric, resulting in a fiber capacitor. These fiber capacitors exhibited a capacitance change of 860 percent when the fiber was stretched 950 percent.

“No presently available material-based strain sensor can operate over nearly as large a strain range,” Liu said. Adding twist to these double-sheath fibers resulted in fast, electrically powered torsional — or rotating — artificial muscles that could be used to rotate mirrors in optical circuits or pump liquids in miniature devices used for chemical analysis, said Dr. Carter Haines BS’11, PhD’15, a research associate in the NanoTech Institute and an author of the paper.

In the laboratory, Nan Jiang, a research associate in the NanoTech Institute, demonstrated that the conducting elastomers can be fabricated in diameters ranging from the very small — about 150 microns, or twice the width of a human hair — to much larger sizes, depending on the size of the rubber core. “Individual small fibers also can be combined into large bundles and plied together like yarn or rope,” she said.

“This technology could be well-suited for rapid commercialization,” said Dr. Raquel Ovalle-Robles MS’06 PhD’08, an author on the paper and chief research and intellectual properties strategist at Lintec of America’s Nano-Science & Technology Center. “The rubber cores used for these sheath-core fibers are inexpensive and readily available,” she said. “The only exotic component is the carbon nanotube aerogel sheet used for the fiber sheath.”

Last year, UT Dallas licensed to Lintec of America a process Baughman’s team developed to transform carbon nanotubes into large-scale structures, such as sheets. Lintec opened its Nano-Science & Technology Center in Richardson, Texas, less than 5 miles from the UT Dallas campus, to manufacture carbon nanotube aerogel sheets for diverse applications.


Story Source:

The above post is reprinted from materials provided by University of Texas, Dallas. Note: Materials may be edited for content and length.

Lehigh 071415 techconnect15Bryan Berger, Himanshu Jain, Chao Zhou and a half dozen other faculty members were invited to give presentations last month at the TechConnect 2015 World Innovation Conference. Lehigh’s participation was organized by the Office of Technology Transfer.

Lehigh scientists and engineers won three National Innovation Awards recently at the TechConnect 2015 World Innovation Conference and National Innovation Showcase held in Washington, D.C.

The awards were for a nanoscale device that captures tumor cells in the blood, a bioengineered enzyme that scrubs microbial biofilms, and a safe, efficient chemical reagent that is stable at room temperature.

Lehigh’s TechConnect initiative was led by the Office of Technology Transfer (OTT) which manages, protects and licenses intellectual property (IP) developed at Lehigh. Yatin Karpe, associate director of the OTT, spearheaded the Lehigh effort and is pursuing IP protection and commercialization for the innovations.

The P.C. Rossin College of Engineering and Applied Science, led by former interim Dean Daniel Lopresti, and the Office of Economic Engagement, led by assistant vice president Cameron McCoy, supported Lehigh’s third-straight appearance at the annual conference.

The three National Innovation Awards were chosen through an industry review of the top 20 percent of annually submitted technologies and based on the potential positive impact the technology would have on industry.

This is the third year in a row that Lehigh has won Innovation Awards. No institution received more than three in 2015.

Lehigh’s National Innovation Awardees were:

•    Yaling Liu, assistant professor of mechanical engineering and mechanics and a member of the bioengineering program, has developed a tiny device that can capture tumor cells circulating in the blood and can potentially indicate disease type, as well as genetic and protein markers that may provide potential treatment options.

•    Bryan Berger, assistant professor of chemical and biomolecular engineering, hopes to improve food safety and keep medical devices clean with an enzyme he’s developed that attacks biofilms.

•    David Vicic, professor and department chair of chemistry, has created a new chemical reagent that is stable at room temperature, potentially eliminating the use of traditional hazardous regents.

TechConnect is one of the largest multi-sector gatherings in the world of technology intellectual property, technology ventures, industrial partners and investors. The event brings together the world’s top technology transfer offices, companies and investment firms to identify the most promising technologies and early stage companies from across the globe.

“This event is a productive opportunity to establish new connections with industry and government partners, many within easy reach of Lehigh,” said Gene Lucadamo, the industry liaison for Lehigh’s Center for Advanced Materials and Nanotechnology and the Lehigh Nanotech Network.

“Some of these connections are with alumni in business or government, and even with nearby Pennsylvania companies that were attracted to Lehigh innovations. These interactions allow us to promote research capabilities and facilities which are available through our Industry Liaison Program, and to identify opportunities for collaborations and funding.”

In addition to the three National Innovator Awards, Lehigh researchers won seven National Innovation Showcase awards and presented five conference papers in areas as diverse as the biomanufacturing of quantum dots, a 3-D imaging technique 20 times faster than current systems, the creation of a miniature medical oxygen concentrator for patients with Chronic Obstructive Pulmonary Disease (COPD), and a biomedically superior bioactive glass that mimics bone.

Attendees include innovators, funding agencies, national and federal labs, international research organizations, universities, tech transfer offices and investment and corporate partners. The 2015 TechConnect World Innovation event encompasses the 2015 SBIR/STTR National Conference, the 2015 National Innovation Summit and Showcase, and Nanotech2015—the world’s largest nanotechnology event.

The following is a list of the Lehigh faculty members who gave presentations at TechConnect 2015:

•    A wavy micropatterned microfluidic device for capturing circulating tumor cells (Principal investigator: Liu)

•    Bioengineered enzymes that safely and cheaply fight bacterial biofilms (Principal investigator: Berger)

•    New reagents for octafluorocyclobutane transfer that eliminate the use of hazardous tetrafluoroethylene (Principal investigator: Vicic)

•    A method to cheaply manufacture quantum dots using bacteria (Principal investigator: Berger)

•    A multiplexing optical coherence tomography technology 20 times faster than current systems that preserves image resolution and allows synchronized cross-sectional and three-dimensional (3D) imaging. (Principal investigator: Chao Zhou, electrical and computer engineering)

•    A miniature medical oxygen concentrator for COPD patients (Principal investigator: Mayuresh Kothare, chemical and biomolecular engineering)

•    A biomedically superior bioactive glass that enables the production of porous bone scaffolds that can be tailored to match the tissue growth rate of a given patient type (Principal investigator: Himanshu Jain, materials science and engineering)

•    A new distributed-feedback technique that dramatically improves the laser beam patterns and increases the output power levels of semiconductor lasers (Principal investigator: Sushil Kumar, electrical and computer engineering)

•    A new pretreatment process to remove unwanted impurities in ceramic powders without any change in the physical properties, leading to better reproducibility of properties and reliability in the final products (Principal investigator: Martin Harmer, materials science and engineering)

Story by Jordan Reese


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