Tag Archives: Yue Zhang

Alleviating joint damage and inflammation from arthritis with neutrophil nanosponges

Assuming you’d be happy with limiting the damage for rheumatoid arthritis, at some point in the future, this research looks promisin. Right now it appears the researchers aren’t anywhere close to a clinical trial. From a Sept. 3, 2018 news item on ScienceDaily,

Engineers at the University of California San Diego [UCSD] have developed neutrophil “nanosponges” that can safely absorb and neutralize a variety of proteins that play a role in the progression of rheumatoid arthritis. Injections of these nanosponges effectively treated severe rheumatoid arthritis in two mouse models. Administering the nanosponges early on also prevented the disease from developing.

A Sept. 3, 2018 UCSD press release (also on EurekAlert), which originated the news item, provides more detail,

“Nanosponges are a new paradigm of treatment to block pathological molecules from triggering disease in the body,” said senior author Liangfang Zhang, a nanoengineering professor at the UC San Diego Jacobs School of Engineering. “Rather than creating treatments to block a few specific types of pathological molecules, we are developing a platform that can block a broad spectrum of them, and this way we can treat and prevent disease more effectively and efficiently.”

This work is one of the latest examples of therapeutic nanosponges developed by Zhang’s lab. Zhang, who is affiliated with the Institute of Engineering in Medicine and Moores Cancer Center at UC San Diego, and his team previously developed red blood cell nanosponges to combat and prevent MRSA infections and macrophage nanosponges to treat and manage sepsis.

neutrophil nanosponge cartoon
Illustration of a neutrophil cell membrane-coated nanoparticle.

The new nanosponges are nanoparticles of biodegradable polymer coated with the cell membranes of neutrophils, a type of white blood cell.

Neutrophils are among the immune system’s first responders against invading pathogens. They are also known to play a role in the development of rheumatoid arthritis, a chronic autoimmune disease that causes painful inflammation in the joints and can ultimately lead to damage of cartilage and bone tissue.

When rheumatoid arthritis develops, cells in the joints produce inflammatory proteins called cytokines. Release of cytokines signals neutrophils to enter the joints. Once there, cytokines bind to receptors on the neutrophil surfaces, activating them to release more cytokines, which in turn draws more neutrophils to the joints and so on.

The nanosponges essentially nip this inflammatory cascade in the bud. By acting as tiny neutrophil decoys, they intercept cytokines and stop them from signaling even more neutrophils to the joints, reducing inflammation and joint damage.

These nanosponges offer a promising alternative to current treatments for rheumatoid arthritis. Some monoclonal antibody drugs, for example, have helped patients manage symptoms of the disease, but they work by neutralizing only specific types of cytokines. This is not sufficient to treat the disease, said Zhang, because there are so many different types of cytokines and pathological molecules involved.

“Neutralizing just one or two types might not be as effective. So our approach is to take neutrophil cell membranes, which naturally have receptors to bind all these different types of cytokines, and use them to manage an entire population of inflammatory molecules,” said Zhang.

“This strategy removes the need to identify specific cytokines or inflammatory signals in the process. Using entire neutrophil cell membranes, we’re cutting off all these inflammatory signals at once,” said first author Qiangzhe Zhang, a Ph.D. student in Professor Liangfang Zhang’s research group at UC San Diego.

To make the neutrophil nanosponges, the researchers first developed a method to separate neutrophils from whole blood. They then processed the cells in a solution that causes them to swell and burst, leaving the membranes behind. The membranes were then broken up into much smaller pieces. Mixing them with ball-shaped nanoparticles made of biodegradable polymer fused the neutrophil cell membranes onto the nanoparticle surfaces.

“One of the major challenges of this work was streamlining this entire process, from isolating neutrophils from blood to removing the membranes, and making this process repeatable. We spent a lot of time figuring this out and eventually created a consistent neutrophil nanosponge production line,” said Qiangzhe Zhang.

In mouse models of severe rheumatoid arthritis, injecting nanosponges in inflamed joints led to reduced swelling and protected cartilage from further damage. The nanosponges performed just as well as treatments in which mice were administered a high dose of monoclonal antibodies.

The nanosponges also worked as a preventive treatment when administered prior to inducing the disease in another group of mice.

Professor Liangfang Zhang cautions that the nanosponge treatment does not eliminate the disease. “We are basically able to manage the disease. It’s not completely gone. But swelling is greatly reduced and cartilage damage is minimized,” he said.

The team hopes to one day see their work in clinical trials.

Here’s a link to and a citation for the paper,

Neutrophil membrane-coated nanoparticles inhibit synovial inflammation and alleviate joint damage in inflammatory arthritis by Qiangzhe Zhang, Diana Dehaini, Yue Zhang, Julia Zhou, Xiangyu Chen, Lifen Zhang, Ronnie H. Fang, Weiwei Gao, & Liangfang Zhang. Nature Nanotechnology (2018) DOI: https://doi.org/10.1038/s41565-018-0254-4 Published 03 September 2018

This paper is behind a paywall.

Thin-film electronic stickers for the Internet of Things (IoT)

This research is from Purdue University (Indiana, US) and the University of Virginia (US) increases and improves the interactivity between objects in what’s called the Internet of Things (IoT).

Caption: Electronic stickers can turn ordinary toy blocks into high-tech sensors within the ‘internet of things.’ Credit: Purdue University image/Chi Hwan Lee

From a July 16, 2018 news item on ScienceDaily,

Billions of objects ranging from smartphones and watches to buildings, machine parts and medical devices have become wireless sensors of their environments, expanding a network called the “internet of things.”

As society moves toward connecting all objects to the internet — even furniture and office supplies — the technology that enables these objects to communicate and sense each other will need to scale up.

Researchers at Purdue University and the University of Virginia have developed a new fabrication method that makes tiny, thin-film electronic circuits peelable from a surface. The technique not only eliminates several manufacturing steps and the associated costs, but also allows any object to sense its environment or be controlled through the application of a high-tech sticker.

Eventually, these stickers could also facilitate wireless communication. …

A July 16, 2018 University of Purdue news release (also on EurekAlert), which originated the news item, explains more,

“We could customize a sensor, stick it onto a drone, and send the drone to dangerous areas to detect gas leaks, for example,” said Chi Hwan Lee, Purdue assistant professor of biomedical engineering and mechanical engineering.

Most of today’s electronic circuits are individually built on their own silicon “wafer,” a flat and rigid substrate. The silicon wafer can then withstand the high temperatures and chemical etching that are used to remove the circuits from the wafer.

But high temperatures and etching damage the silicon wafer, forcing the manufacturing process to accommodate an entirely new wafer each time.

Lee’s new fabrication technique, called “transfer printing,” cuts down manufacturing costs by using a single wafer to build a nearly infinite number of thin films holding electronic circuits. Instead of high temperatures and chemicals, the film can peel off at room temperature with the energy-saving help of simply water.

“It’s like the red paint on San Francisco’s Golden Gate Bridge – paint peels because the environment is very wet,” Lee said. “So in our case, submerging the wafer and completed circuit in water significantly reduces the mechanical peeling stress and is environmentally-friendly.”

A ductile metal layer, such as nickel, inserted between the electronic film and the silicon wafer, makes the peeling possible in water. These thin-film electronics can then be trimmed and pasted onto any surface, granting that object electronic features.

Putting one of the stickers on a flower pot, for example, made that flower pot capable of sensing temperature changes that could affect the plant’s growth.

Lee’s lab also demonstrated that the components of electronic integrated circuits work just as well before and after they were made into a thin film peeled from a silicon wafer. The researchers used one film to turn on and off an LED light display.

“We’ve optimized this process so that we can delaminate electronic films from wafers in a defect-free manner,” Lee said.

This technology holds a non-provisional U.S. patent. The work was supported by the Purdue Research Foundation, the Air Force Research Laboratory (AFRL-S-114-054-002), the National Science Foundation (NSF-CMMI-1728149) and the University of Virginia.

The researchers have provided a video,

Here’s a link to and a citation for the paper,

Wafer-recyclable, environment-friendly transfer printing for large-scale thin-film nanoelectronics by Dae Seung Wie, Yue Zhang, Min Ku Kim, Bongjoong Kim, Sangwook Park, Young-Joon Kim, Pedro P. Irazoqui, Xiaolin Zheng, Baoxing Xu, and Chi Hwan Lee.
PNAS July 16, 2018 201806640 DOI: https://doi.org/10.1073/pnas.1806640115
published ahead of print July 16, 2018

This paper is behind a paywall.

Dexter Johnson provides some context in his July 25, 2018 posting on the Nanoclast blog (on the IEEE [Institute of Electronic and Electrical Engineers] website), Note: A link has been removed,

The Internet of Things (IoT), the interconnection of billions of objects and devices that will be communicating with each other, has been the topic of many futurists’ projections. However, getting the engineering sorted out with the aim of fully realizing the myriad visions for IoT is another story. One key issue to address: How do you get the electronics onto these devices efficiently and economically?

A team of researchers from Purdue University and the University of Virginia has developed a new manufacturing process that could make equipping a device with all the sensors and other electronics that will make it Internet capable as easily as putting a piece of tape on it.

… this new approach makes use of a water environment at room temperature to control the interfacial debonding process. This allows clean, intact delamination of prefabricated thin film devices when they’re pulled away from the original wafer.

The use of mechanical peeling in water rather than etching solution provides a number of benefits in the manufacturing scheme. Among them are simplicity, controllability, and cost effectiveness, says Chi Hwan Lee, assistant professor at Purdue University and coauthor of the paper chronicling the research.

If you have the time, do read Dexter’s piece. He always adds something that seems obvious in retrospect but wasn’t until he wrote it.

Changing the vibration of gold nanodisks (acoustic tuning) with light

A May 7, 2015 news item on phys.org describes research that could have a major impact on photonics applications,

In a study that could open doors for new applications of photonics from molecular sensing to wireless communications, Rice University [Texas, US] scientists have discovered a new method to tune the light-induced vibrations of nanoparticles through slight alterations to the surface to which the particles are attached.

n a study published online this week in Nature Communications, researchers at Rice’s Laboratory for Nanophotonics (LANP) used ultrafast laser pulses to induce the atoms in gold nanodisks to vibrate. These vibrational patterns, known as acoustic phonons, have a characteristic frequency that relates directly to the size of the nanoparticle. The researchers found they could fine-tune the acoustic response of the particle by varying the thickness of the material to which the nanodisks were attached.

A May 7, 2015 Rice University news release (also on EurekAlert), which originated the news item, expands on the theme (Note: A link has been removed),

Our results point toward a straightforward method for tuning the acoustic phonon frequency of a nanostructure in the gigahertz range by controlling the thickness of its adhesion layer,” said lead researcher Stephan Link, associate professor of chemistry and in electrical and computer engineering.

Light has no mass, but each photon that strikes an object imparts a miniscule amount of mechanical motion, thanks to a phenomenon known as radiation pressure. A branch of physics known as optomechanics has developed over the past decade to study and exploit radiation pressure for applications like gravity wave detection and low-temperature generation.

Link and colleagues at LANP specialize in another branch of science called plasmonics that is devoted to the study of light-activated nanostructures. Plasmons are waves of electrons that flow like a fluid across a metallic surface.

When a light pulse of a specific wavelength strikes a metal particle like the puck-shaped gold nanodisks in the LANP experiments, the light energy is converted into plasmons. These plasmons slosh across the surface of the particle with a characteristic frequency, in much the same way that each phonon has a characteristic vibrational frequency.

The study’s first author, Wei-Shun Chang, a postdoctoral researcher in Link’s lab, and graduate students Fangfang Wen and Man-Nung Su conducted a series of experiments that revealed a direct connection between the resonant frequencies of the plasmons and phonons in nanodisks that had been exposed to laser pulses.

“Heating nanostructures with a short light pulse launches acoustic phonons that depend sensitively on the structure’s dimensions,” Link said. “Thanks to advanced lithographic techniques, experimentalists can engineer plasmonic nanostructures with great precision. Based on our results, it appears that plasmonic nanostructures may present an interesting alternative to conventional optomechanical oscillators.”

Chang said plasmonics experts often rely on substrates when using electron-beam lithography to pattern plasmonic structures. For example, gold nanodisks like those used in the experiments will not stick to glass slides. But if a thin substrate of titanium or chromium is added to the glass, the disks will adhere and stay where they are placed.

“The substrate layer affects the mechanical properties of the nanostructure, but many questions remain as to how it does this,” Chang said. “Our experiments explored how the thickness of the substrate impacted properties like adhesion and phononic frequency.”

Link said the research was a collaborative effort involving research groups at Rice and the University of Melbourne in Victoria, Australia.

“Wei-Shun and Man-Nung from my lab did the ultrafast spectroscopy,” Link said. “Fangfang, who is in Naomi Halas’ group here at Rice, made the nanodisks. John Sader at the University of Melbourne, and his postdoc Debadi Chakraborty calculated the acoustic modes, and Yue Zhang, a Rice graduate student from Peter Nordlander’s group at Rice simulated the optical/plasmonic properties. Bo Shuang of the Landes’ research group at Rice contributed to the analysis of the experimental data.”

Here’s a link to and a citation for the paper,

Tuning the acoustic frequency of a gold nanodisk through its adhesion layer by Wei-Shun Chang, Fangfang Wen, Debadi Chakraborty, Man-Nung Su, Yue Zhang, Bo Shuang, Peter Nordlander, John E. Sader, Naomi J. Halas, & Stephan Link. Nature Communications 6, Article number: 7022 doi:10.1038/ncomms8022 Published 05 May 2015

This paper is behind a paywall but a free preview is available vie ReadCube Access.