Covid-19 Diagnostic Based on MIT Technology to be Tested on Patients Soon


MIT-Covid-Research-Roundup-01_0

This scanning electron microscope image shows SARS-CoV-2 (yellow)—also known as 2019-nCoV, the virus that causes COVID-19—isolated from a patient, emerging from the surface of cells (blue/pink) cultured in the lab. Image: NIAID-RML

A variety of MIT research projects could aid efforts to detect and prevent the spread of coronavirus.

As more Covid-19 cases appear in the United States and around the world, the need for fast, easy-to-use diagnostic tests is becoming ever more pressing. A startup company spun out from MIT is now working on a paper-based test that can deliver results in under half an hour, based on technology developed at MIT’s Institute for Medical Engineering and Science (IMES).

Cambridge-based E25Bio, which developed the test, is now preparing to submit it to the FDA for “emergency use authorization,” which would grant temporary approval for using the device on patient samples during public health emergencies.

Elsewhere around MIT, several other research groups are working on projects that may help further scientists’ understanding of how coronaviruses are transmitted and how infection may be prevented. Their work touches on fields ranging from diagnostics and vaccine development to more traditional disease prevention measures such as social distancing and handwashing.

Faster diagnosis

The technology behind the new E25Bio diagnostic was developed by Lee Gehrke, the Hermann L.F. von Helmholtz Professor at IMES, and other members of his lab, including Irene Bosch, a former IMES research scientist who is now the CTO of E25Bio.

For the past several years, Gehrke, Bosch, and others in the lab have been working on diagnostic devices that work similar to a pregnancy test but can identify viral proteins from patient samples. The researchers have used this technology, known as lateral flow technology, to create tests for Ebola, dengue fever, and Zika virus, among other infectious diseases.

The tests consist of strips of paper that are coated with antibodies that bind to a specific viral protein. A second antibody is attached to specialized nanoparticles, and the patient’s sample is added to a solution of those particles. The test strip is then dipped in this solution. If the viral protein is present, it attaches to the antibodies on the paper strip as well as the nanoparticle-bound antibodies, and a colored spot appears on the strip within 20 minutes.

Currently, there are two primary types of Covid-19 diagnostics available. One such test screens patient blood samples for antibodies against the virus. However, antibodies are often not detectable until a few days after symptoms begin. Another type of test looks for viral DNA in a sputum sample. These tests can detect the virus earlier in the infection, but they require polymerase chain reaction (PCR), a technology that amplifies the amount of DNA to detectable levels and takes several hours to perform.

“Our hope is that, similar to other tests that we’ve developed, this will be usable on the day that symptoms develop,” Gehrke says. “We don’t have to wait for antibodies to the virus to come up.”

If the U.S. Food and Drug Administration grants the emergency authorization, E25Bio could start testing the diagnostic with patient samples, which they haven’t been able to do yet. “If those are successful, then the next step would be to talk about using it for actual clinical diagnosis,” Gehrke says.

Another advantage of this approach is that the paper tests can be easily and inexpensively manufactured in large quantities, he adds.

RNA vaccines

On Feb. 24, only about a month after the first U.S. case of coronavirus was reported, the Cambridge-based biotech company Moderna announced it had an experimental vaccine ready to test. That speedy turnaround is due to the unique advantages of RNA vaccines, says Daniel Anderson, an MIT professor of chemical engineering, who also works on such vaccines, though not specifically for coronavirus.

“A key advantage of messenger RNA is the speed with which you can identify a new sequence and use it to come up with a new vaccine,” Anderson says.

Traditional vaccines consist of an inactivated form of a viral protein that induces an immune response. However, these vaccines usually take a long time to manufacture, and for some diseases, they are too risky. Vaccines that consist of messenger RNA are an appealing alternative because they induce host cells to produce many copies of the proteins they encode, provoking a stronger immune response than proteins delivered on their own.

RNA vaccines can also be quickly reprogrammed to target different viral proteins, as long as the sequence encoding the protein is known. The main obstacle to developing such vaccines so far has been finding effective and safe ways to deliver them. Anderson’s lab has been working on such strategies for several years, and in a recent study he showed that packing such vaccines into a special type of lipid nanoparticles can enhance the immune response that they produce.

“Messenger RNA can encode the viral antigens, but in order to work, we need to find a way to deliver these antigens to the correct part of the body so that they get expressed and generate an immune response. We also need to make sure that the vaccine causes appropriate immune stimulation to get a strong response,” Anderson says.

Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), has estimated that it will take at least 12 to 18 months to fully test any potential Covid-19 vaccine for safety and effectiveness.

Keep your distance

Over the last decade, Lydia Bourouiba, an associate professor directing the Fluid Dynamics of Disease Transmission Laboratory at MIT, has focused on characterizing and modeling infectious disease dynamics and transmission at various scales. Through experiments in the lab and clinical environment, she has reported that when a person coughs or sneezes, they do not emit a spray of individual droplets that quickly fall to the ground and evaporate, as scientists had once thought. Instead, they produce a complex cloud of hot and moist air that traps droplets of all sizes together, propelling them much further through the air than any individual droplet would travel on its own.

On average, her experiments have revealed that a cough can transmit droplets up to 13 to 16 feet, while a sneeze can eject them up to 26 feet away. Surrounding air conditions can act to further disperse the residual droplets in upper levels of rooms.

Bourouiba notes that the presence of the high-speed gas cloud is independent of the type of organism or pathogen that the cloud may contain. The droplets within it depend on pathogenesis coupled with a patient’s physiology — a combination which her laboratory has focused on deciphering in the context of influenza. She is now expanding her studies and modeling to translate the work to Covid-19, and says now is a critical time to invest in research.

“This virus is going to stay with us for a while — and certainly data suggest that it is not going to suddenly disappear when the weather changes,” she says. “There’s a fine and important balance between safety, precautions and action that is important to strike to enable and dramatically accelerate research to be done now so we can be better prepared and informed for actions in the weeks and months to come when the worst of the pandemic will unfold.”

She is also working with others to evaluate ways to limit a cloud’s dispersal and slow Covid-19 transmission to health care workers and others in shared spaces. “A surgical mask is not protective against inhalation of a pathogen from the cloud,” she says. “For an infected patient wearing it, it can contain some of the forward ejecta from coughs or sneezes, but these are very violent ejections and masks are completely open on all sides, and fluid flows through the path of least resistance.”

Based on the data, she recommends that health care workers consider wearing a respirator, whenever possible. And, for the general public, Bourouiba emphasizes that the risk of contracting COVID-19 remains relatively low locally, and that risk should be thought of in the context of the community.

Wash those hands

Another good way to protect yourself against all of those tiny infectious droplets is to wash your hands. (Again, and again, and again.)

Ruben Juanes, an MIT professor of civil and environmental engineering, and of earth, atmospheric and planetary sciences, published a study in December showing the importance of improving rates of handwashing at key airports in order to curtail the spread of an epidemic. Now, he says, following the Covid-19 outbreak, governments around the world have imposed unprecedented restrictions on mobility, including the closure of airports and suspension of flight routes.

At the same time, the World Health Organization, U.S. Centers for Disease Control, and many other health agencies all recommend hand-hygiene as the number one precaution measure against disease spread. “Following our recent paper on the impact of hand-hygiene on global disease spreading,” Juanes says, “we are now investigating the combined effect of restrictions on human mobility and enhanced engagement with hand-hygiene on the global spread of COVID-19 through the world air-transportation network.”

Juanes says he and Christos Nicolaides PhD ’14, a professor at the University of Cyprus who was the lead author of the previous study, are working “with fine-grained, worldwide air-traffic data that accounts for all flights for the period between Jan. 15, 2020 until today (accounting for closures/cancellations) and the corresponding period of 2019 (base level) to elucidate the role of travel restrictions on the global spread of Covid-19 through detailed epidemiological modeling.”

“Furthermore,” he adds, “we simulate different hand-hygiene strategies at airports on top of travel restrictions with the goal of proposing an optimal strategy that combines travel restrictions and enhanced hand hygiene, to mitigate the advance of Covid-19 both in the short term (weeks) and the long term (the next flu season).”

Juanes says they will make the results immediately available via medarXiv, while the work follows peer-review in a journal. This would also allow the information to reach other academic and government institutions in a more timely way, he says.

What’s Coming: DARPA is Eyeing a High-Tech Contact Lens Straight Out of ‘Mission: Impossible’


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The Defense Advanced Research Projects Agency (DARPA) is reportedly interested in a new wirelessly-connected contact lens recently unveiled in France, the latest in the agency’s ongoing search for small-scale technology to augment U.S. service members’ visual capabilities in the field.

Researchers at leading French engineering IMT Atlantique in mid-April announced “the first autonomous contact lens incorporating a flexible micro-battery,” a lightweight lens capable of not only providing augmented vision assistance to users but relaying visual information wirelessly — not unlike, say, the lens Jeremy Renner uses in Mission: Impossible – Ghost Protocol to scan a batch of nuclear codes: (Watch)

More importantly, the new lens can perform its functions without a bulky external power supply, capable of “continuously supply[ing] a light source such as a light-emitting diode (LED) for several hours,” according to the IMT Atlantique announcement.

“Storing energy on small scales is a real challenge,” said Thierry Djenizian, head of the Flexible Electronics Department at the Centre Microélectronique de Provence Georges Charpak and co-head of the p

The lens was primarily designed for medical and automotive applications, but according to French business magazine L’Usine Nouvelle (‘The New Factory’), the lens has garnered interest from both DARPA and Microsoft, which was recently contracted by the the U.S. Army to furnish soldiers with with its HoloLens augmented reality headset.

DARPA’s been on the hunt for a high-tech eyepiece more than a decade, and the agency has funded several similar projects in recent years.

In January 2012, DARPA announced that U.S.-based tech firm Innovega was developing “iOptiks” contact lenses designed to enhance normal vision by projecting digital images onto a standard pair of eyeglasses like a miniaturized heads-up display, “allow[ing] a wearer to view virtual and augmented reality images without the need for bulky apparatus,” as the agency put it.

Three years later, researchers at Switzerland’s École Polytechnique Fédérale de Lausanne (EPFL) unveiled a DARPA-funded contact lens that “magnifies objects at the wink of an eye,” The Guardian reported, although researchers concluded that the technology was better suited for age-related visual deterioration rather than battlefield applications.

“[DARPA researchers] were really interested in supervision, but the reality is more tame than that,” researcher Eric Tremblay told the American Association for the Advancement of Science at the time.

These past projects, like most other blue sky research projects pursued by the DARPA, have likely informed the Pentagon’s research and development of augmented reality tech that U.S. military planners have increasingly pursued in recent years. And the technology is only poised to improve: as Wired recently reported, big tech companies like Google, Sony, and Samsung are all pushing the envelope when it comes to consumer-marketxed augmented vision tech.

But when “smart” contact lenses will actually hit Pentagon armories, like most futuristic DARPA efforts, remains to be seen. In the meantime, it looks like U.S. service members in search of enhanced vision will have to stick to their “birth control glasses.”

This article by Jared Keller originally appeared at Task & Purpose. Follow Task & Purpose onTwitter. This article first appeared in 2019.

Hairy nano-cellulose provides green anti-scaling solution – More applications including drug delivery, antimicrobial agents, and fluorescent dyes for medical imaging – McGill University


hairynanotecCredit: McGill University

A new type of cellulose nanoparticle, invented by McGill University researchers, is at the heart of a more effective and less environmentally damaging solution to one of the biggest challenges facing water-based industries: preventing the buildup of scale.

Formed by the accumulation of sparingly soluble minerals, scale can seriously impair the operation of just about any equipment that conducts or stores water – from household appliances to industrial installations. Most of the anti-scaling agents currently in use are high in phosphorus derivatives, environmental pollutants that can have catastrophic consequences for aquatic ecosystems.

In a series of papers published in the Royal Society of Chemistry’s Materials Horizons and the American Chemical Society’s Applied Materials & Interfaces, a team of McGill chemists and chemical engineers describe how they have developed a phosphorus-free anti-scaling solution based on a nanotechnology breakthrough with an unusual name: hairy nanocellulose.

An unlikely candidate

Lead author Amir Sheikhi, now a postdoctoral fellow in the Department of Bioengineering at the University of California, Los Angeles, says despite its green credentials  was not an obvious place to look for a way to fight scale.

“Cellulose is the most abundant biopolymer in the world. It’s renewable and biodegradable. But it’s probably one of the least attractive options for an anti-scaling agent because it’s neutral, it has no charged functional groups,” he says.

While working as a postdoctoral fellow with McGill chemistry professor Ashok Kakkar, Sheikhi developed a number of macromolecular antiscalants that were more effective than products widely used in industry – but all of his discoveries were phosphonate-based. His desire to push his research further and find a phosphorus-free alternative led him to take a closer look at cellulose.

“Nanoengineered hairy cellulose turned out to work even better than the phosphonated molecules,” he says.

The breakthrough came when the research team succeeded in nanoengineering negatively charged carboxyl groups onto cellulose nanoparticles. The result was a particle that was no longer neutral, but instead carried charged functional groups capable of controlling the tendency of positively charged calcium ions to form scale.

Hirsute wonder particle a chance discovery

Previous attempts to functionalize cellulose in this way focused on two earlier forms of nanoparticle – cellulose nanofibrils and . But these efforts produced only a minimal amount of useful product. The difference this time was that the McGill team worked with hairy nanocellulose – a new nanoparticle first discovered in the laboratory of McGill chemistry professor Theo van de Ven.

Van de Ven, who also participated in the anti-scaling research, recalls the moment in 2011 when Han Yang, then a doctoral student in his lab, stumbled upon the new form of nanocellulose.

“He came into my office with a test tube that looked like it had water in it and he said, ‘Sir! My suspension has disappeared!'” van de Ven says with a grin.

“He had a white suspension of kraft fibres and it had turned transparent. When something is transparent, you know immediately it has either dissolved or turned nano. We performed a number of characterizations and we realized he had made a new form of nanocellulose.”

Extreme versatility

The secret to making hairy nanocellulose lies in cutting cellulose nanofibrils – which are made up of an alternating series of crystalline and amorphous regions – at precise locations to produce nanoparticles with amorphous regions sprouting from either end like so many unruly strands of hair.

“By breaking the nanofibrils up the way we do, you get all these cellulose chains sticking out which are accessible to chemicals,” van de Ven explains. “That’s why our nanocellulose can be functionalized to a far greater extent than other kinds.”

Given the chemical versatility of hairy nanocellulose, the research team sees strong potential for applications beyond anti-scaling, including drug delivery, antimicrobial agents, and fluorescent dyes for medical imaging.

“We can link just about any molecule you can think of to hairy ,” van de Ven says.

 Explore further: Ready-to-use recipe for turning plant waste into gasoline

More information: Amir Sheikhi et al. Overcoming Interfacial Scaling Using Engineered Nanocelluloses: A QCM-D Study, ACS Applied Materials & Interfaces (2018). DOI: 10.1021/acsami.8b07435

Amir Sheikhi et al. Nanoengineering colloidal and polymeric celluloses for threshold scale inhibition: towards universal biomass-based crystal modification, Materials Horizons (2018). DOI: 10.1039/C7MH00823F

 

A new brain-inspired architecture could improve how computers handle data and advance AI


anewbraininsBrain-inspired computing using phase change memory. Credit: Nature Nanotechnology/IBM Research

IBM researchers are developing a new computer architecture, better equipped to handle increased data loads from artificial intelligence. Their designs draw on concepts from the human brain and significantly outperform conventional computers in comparative studies. They report on their recent findings in the Journal of Applied Physics.

Today’s computers are built on the von Neumann architecture, developed in the 1940s. Von Neumann computing systems feature a central processor that executes logic and arithmetic, a memory unit, storage, and input and output devices. Unlike the stovepipe components in conventional computers, the authors propose that brain-inspired computers could have coexisting processing and memory units.

Abu Sebastian, an author on the paper, explained that executing certain  in the computer’s memory would increase the system’s efficiency and save energy.

“If you look at human beings, we compute with 20 to 30 watts of power, whereas AI today is based on supercomputers which run on kilowatts or megawatts of power,” Sebastian said. “In the brain, synapses are both computing and storing information. In a new architecture, going beyond von Neumann, memory has to play a more active role in computing.”

The IBM team drew on three different levels of inspiration from the brain. The first level exploits a memory ‘s state dynamics to perform computational tasks in the memory itself, similar to how the brain’s memory and processing are co-located. The second level draws on the brain’s synaptic network structures as inspiration for arrays of phase change memory (PCM) devices to accelerate training for deep neural networks. Lastly, the dynamic and stochastic nature of neurons and synapses inspired the team to create a powerful computational substrate for spiking neural networks.

Phase change memory is a nanoscale memory device built from compounds of Ge, Te and Sb sandwiched between electrodes. These compounds exhibit different electrical properties depending on their atomic arrangement. For example, in a disordered phase, these materials exhibit high resistivity, whereas in a crystalline phase they show low resistivity.

By applying electrical pulses, the researchers modulated the ratio of material in the crystalline and the amorphous phases so the phase change memory devices could support a continuum of electrical resistance or conductance. This analog storage better resembles nonbinary, biological synapses and enables more information to be stored in a single nanoscale device.

Sebastian and his IBM colleagues have encountered surprising results in their comparative studies on the efficiency of these proposed systems. “We always expected these systems to be much better than conventional computing systems in some tasks, but we were surprised how much more efficient some of these approaches were.”

Last year, they ran an unsupervised machine learning algorithm on a conventional  and a prototype computational memory platform based on  change  devices. “We could achieve 200 times faster performance in the  computing systems as opposed to conventional computing systems.” Sebastian said. “We always knew they would be efficient, but we didn’t expect them to outperform by this much.” The team continues to build prototype chips and systems based on brain-inspired concepts.

 Explore further: Novel synaptic architecture for brain inspired computing

More information: Hiroto Kase et al, Biosensor response from target molecules with inhomogeneous charge localization, Journal of Applied Physics (2018). DOI: 10.1063/1.5036538

 

In one-two punch, researchers load ‘nanocarriers’ to deliver cancer-fighting drugs and imaging molecules to tumors


nano-carriers-161129161516_1_540x360Zhang’s group created this nanocarrier using a “load during assembly” approach, shown along the top. Images b, c and d are microscopic views of the nanocarriers at each major step of the assembly and loading process. Credit: Miqin Zhang

In one-two punch, researchers load ‘nanocarriers’ to deliver cancer-fighting drugs and imaging molecules to tumors

A conundrum of cancer is the tumor’s ability to use our bodies as human shields to deflect treatment. Tumors grow among normal tissues and organs, often giving doctors few options but to damage, poison or remove healthy parts of our body in attempts to beat back the cancer with surgery, chemotherapy or radiation.

But in a paper published Sept. 27 in the journal Small, scientists at the University of Washington describe a new system to encase chemotherapy drugs within tiny, synthetic “nanocarrier” packages, which could be injected into patients and disassembled at the tumor site to release their toxic cargo.

The group, led by UW professor of materials science and engineering Miqin Zhang, is not the first to work on nanocarriers. But the nanocarrier package developed by Zhang’s team is a hybrid of synthetic materials, which gives the nanocarrier the unique ability to ferry not just drugs, but also tiny fluorescent or magnetic particles to stain the tumor and make it visible to surgeons.

“Our nanocarrier system is really a hybrid addressing two needs — drug delivery and tumor imaging,” said Zhang, who is senior author on the paper. “First, this nanocarrier can deliver chemotherapy drugs and release them in the tumor area, which spares healthy tissue from toxic side effects. Second, we load the nanocarrier with materials to help doctors visualize the tumor, either using a microscope or by MRI scan.”

Their hybrid nanocarrier builds on years of research into the types of synthetic materials that could package drugs for delivery into a specific part of a patient’s body. In previous attempts, scientists would often first try make an empty nanocarrier out of a synthetic material. Once assembled, they would load the nanocarrier with a therapeutic drug. But this approach was inefficient, and carried a high risk of damaging the fragile drugs and rendering them ineffective.

“Most chemotherapy drugs have complex structures — essentially, they’re very fragile — and they do no good if they are broken by the time they reach the tumor,” said Zhang.

Nano Body II 43a262816377a448922f9811e069be13Zhang’s team worked around this problem by designing a nanocarrier that could be assembled and loaded simultaneously. Their approach is akin to laying cargo within a shipping container even as the container’s walls, floor and roof are being assembled and bolted together.

This “load during assembly” technique also let Zhang’s team incorporate multiple chemical components into the nanocarrier’s structure, which could help hold cargo in place and make the tumor easy to image in clinical settings.

Their nanocarrier sports a core of iron oxide, which provides structure but can also be used as an imaging agent in MRI scans. A shell of silica surrounds the core, and was designed to efficiently stack the chemotherapy drug paclitaxel. They also included space in the nanocarrier for carbon dots, tiny particles that can “stain” tissue and make it easier to see under a microscope, helping doctors resolve the boundaries between cancerous and healthy tissue for further treatment or surgery. The intensity of many imaging agents fades over time, but Zhang said this nanocarrier can provide sustained imaging for months.

Yet despite holding so much cargo, the fully loaded nanocarriers are less than the thickness of a sheet of flimsy notebook paper.

The silica shell keeps the nanocarriers watertight. In addition, they do not interfere with healthy tissue, as Zhang’s team showed by injecting healthy mice with empty nanocarriers or nanocarriers loaded with drug cargo. Five days after injection, they checked vital organs in the mice for evidence of toxicity and found none.

“This would indicate that the nanocarriers themselves do not trigger an adverse reaction in the body, and that the loaded nanocarriers are keeping their toxic cargo shielded from the body,” said Zhang.

The UW team also designed the nanocarriers to be easily disassembled once they reached a desired location. Gentle heating from low-level infrared light was sufficient to make the nanocarriers break apart and disgorge their cargo, which is something doctors could apply to the tumor site during treatment.

As their final test of the nanocarrier effectiveness, Zhang’s team turned to mice with a form of transmissible cancer. Mice that they injected with empty nanocarriers showed no reduction in tumor size. But tumors shrank significantly in mice injected with nanocarriers that were loaded with paclitaxel. They saw a similar affect on human cancer cells cultured and tested in the lab.

“These results show that the nanocarriers can deliver their cargo intact to the tumor site,” said Zhang. “And while we designed this nanocarrier specifically to accommodate paclitaxel, it is possible to adjust this technique for other drugs.”

There are still mountains to climb before this technology is proven safe and effective for humans. But Zhang hopes her team’s approach and promising results will accelerate the ascent.


Story Source:

Materials provided by University of Washington. Original written by James Urton. Note: Content may be edited for style and length.


Journal Reference:

  1. Hui Wang, Kui Wang, Bowei Tian, Richard Revia, Qingxin Mu, Mike Jeon, Fei-Chien Chang, Miqin Zhang. Preloading of Hydrophobic Anticancer Drug into Multifunctional Nanocarrier for Multimodal Imaging, NIR-Responsive Drug Release, and Synergistic Therapy. Small, 2016; DOI: 10.1002/smll.201602263

Quantum Bit MRI Machine to See Shapes of Individual Biomolecules for Drug Research


quantum-mri

 

Drug discovery is a long and difficult process that requires a comprehensive understanding of the molecular structures of compounds under investigation. It’s difficult to have an idea of the precise shape of complex molecules such as proteins, but researchers at University of Melbourne in Australia have come up with a way of seeing the location of individual atoms within biomolecules.

Using quantum bits, most notably utilized in quantum computer research, the investigators offer a way of producing a magnetic resonance sensor and a magnetic field gradient that can work as a tiny MRI machine. The machine would have the resolution capable of seeing single atoms components of larger molecules. This MRI machine has yet to be actually built, but the steps have been laid out based on comprehensive theoretical work. If it proves successful in practice, the technology may overcome current imaging techniques that rely on statistical averages and don’t work well on molecules that don’t crystallize well.

“In a conventional MRI machine large magnets set up a field gradient in all three directions to create 3D images; in our system we use the natural magnetic properties of a single atomic qubit,” said lead author of the research Viktor Perunicic. “The system would be fabricated on-chip, and by carefully controlling the quantum state of the qubit probe as it interacts with the atoms in the target molecule, we can extract information about the positions of atoms by periodically measuring the qubit probe and thus create an image of the molecule’s structure.”

From the study abstract in Nature Communications:

Signals corresponding to specific regions of the molecule’s nuclear spin density are encoded on the quantum state of the probe, which is used to produce a 3D image of the molecular structure. Quantum simulations of the protocol applied to the rapamycin molecule (C51H79NO13) show that the hydrogen and carbon substructure can be imaged at the angstrom level using current spin-probe technology. With prospects for scaling to large molecules and/or fast dynamic conformation mapping using spin labels, this method provides a realistic pathway for single-molecule microscopy.

Read More …

Study in Nature Communications: A quantum spin-probe molecular microscope…

 

 

Quantum dots with impermeable shell used as a powerful tool for “nano-engineering”


QDs Shell 081116 160811101152_1_540x360Images of ZnO quantum dots prepared by the Institute of Physical Chemistry of the Polish Academy of Sciences in Warsaw, taken by transmission electron microscopy. False colors.
Credit: IPC PAS

Unique optical features of quantum dots make them an attractive tool for many applications, from cutting-edge displays to medical imaging. Physical, chemical or biological properties of quantum dots must, however, be adapted to the desired needs.

Unfortunately, up to now quantum dots prepared by chemical methods could only be functionalized using copper-based click reactions with retention of their luminescence. This obstacle can be ascribed to the fact that copper ions destroy the ability of quantum dots to emit light. Scientists from the Institute of Physical Chemistry of the Polish Academy of Sciences (IPC PAS) in Warsaw and the Faculty of Chemistry of the Warsaw University of Technology (FC WUT) have shown, however, that zinc oxide (ZnO) quantum dots prepared by an original method developed by them, after modification by the click reaction with the participation of copper ions, fully retain their ability to emit light.

“Click reactions catalyzed by copper cations have long attracted the attention of chemists dealing with quantum dots. The experimental results, however, were disappointing: after modification, the luminescence was so poor that they were just not fit for use. We were the first to demonstrate that it is possible to produce quantum dots from organometallic precursors in a way they do not lose their valuable optical properties after being subjected to copper-catalysed click reactions,” says Prof. Janusz Lewinski (IPC PAS, FC WUT).

Quantum dots are crystalline structures with size of a few nanometers (billionth parts of a meter). As semiconductor materials, they exhibit a variety of interesting features typical of quantum objects, including absorbing and emitting radiation of only a strictly defined energy. Since atoms interact with light in a similar way, quantum dots are often called artificial atoms. In some respects, however, quantum dots offer more possibilities than atoms. Optical properties of each dot actually depend on its size and the type of material from which it is formed. This means that quantum dots may be precisely designed for specific applications.

To meet the need of specific applications, quantum dots have to be tailored in terms of physico-chemical properties. For this purpose, chemical molecules with suitable characteristics are attached to their surface. Due to the simplicity, efficacy, and speed of the process, an exceptionally convenient method is the click reaction. Unfortunately, one of the most widely used click reactions takes place with the participation of copper ions, which was reported to result in the almost complete quenching of the luminescence of the quantum dots.

“Failure is usually a result of the inadequate quality of quantum dots, which is determined by the synthesis method. Currently, ZnO dots are mainly produced by the sol-gel method from inorganic precursors. Quantum dots generated in this manner are coated with a heterogeneous and probably leaky protective shell, made of various sorts of chemical molecules. During a click reaction, the copper ions are in direct contact with the surface of quantum dots and quench the luminescence of the dot, which becomes completely useless,” explains Dr. Agnieszka Grala (IPC PAS), the first author of the article in the Chemical Communications journal.

For several years, Prof. Lewinski’s team has been developing alternative methods for the preparation of high quality ZnO quantum dots. The method presented in this paper affords the quantum dots derived from organozinc precursors. Composition of the nanoparticles can be programmed at the stage of precursors preparation, which makes it possible to precisely control the character of their organic-inorganic interface.

“Nanoparticles produced by our method are crystalline and all have almost the same size. They are spherical and have characteristics of typical quantum dots. Every nanoparticle is stabilized by an impermeable protective jacket, built of organic compounds, strongly anchored on the surface of the semiconductor core. As a result, our quantum dots remain stable for a long time and do not aggregate, that is clump together, in solutions,” describes Malgorzata Wolska-Pietkiewicz, a PhD student at FC WUT.

“The key to success is producing a uniform stabilizing shell. Such coatings are characteristic of the ZnO quantum dots obtained by our method. The organic layer behaves as a tight protective umbrella protecting dots from direct influence of the copper ions,” says Dr. Grala and clarifies: “We carried out click reaction known as alkyne-azide cycloaddition, in which we used a copper(l) compound as catalysts. After functionalization, our quantum dots shone as brightly as at the beginning.”

Quantum dots keep finding more and more applications in various industrial processes and as nanomarkers in, among others, biology and medicine, where they are combined with biologically active molecules. Nanoobjects functionalized in this manner are used to label both individual cells as well as whole tissues. The unique properties of quantum dots also enable long-term monitoring of the labelled item. Commonly used quantum dots, however, contain toxic heavy metals, including cadmium. In addition, they clump together in solutions, which supports the thesis of the lack of tightness of their shells. Meanwhile, the ZnO dots produced by Prof. Lewinski’s group are non-toxic, they do not aggregate, and can be bound to many chemical compounds — so they are much more suitable for medical diagnosis and for imaging cells and tissues.

Research on the methods of production of functionalized ZnO quantum dots was carried out under an OPUS grant from the Poland’s National Science Centre.


Story Source:

The above post is reprinted from materials provided by Institute of Physical Chemistry of the Polish Academy of Sciences.Note: Content may be edited for style and length.


Journal Reference:

  1. Agnieszka Grala, Małgorzata Wolska-Pietkiewicz, Wojciech Danowski, Zbigniew Wróbel, Justyna Grzonka, Janusz Lewiński. ‘Clickable’ ZnO nanocrystals: the superiority of a novel organometallic approach over the inorganic sol–gel procedure. Chem. Commun., 2016; 52 (46): 7340 DOI:10.1039/C6CC01430E

Lehigh University: First single-Enzyme Method to mass-produce Quantum Dots: significantly quicker, cheaper and greener production method


Lehigh QDs 051016 firstsinglee

Tubes filled with quantum dots produced in the Lehigh University lab. Credit: Christa Neu/Lehigh University Communications + Public Affairs

Quantum dots (QDs) are semiconducting nanocrystals prized for their optical and electronic properties. The brilliant, pure colors produced by QDs when stimulated with ultraviolet light are ideal for use in flat screen displays, medical imaging devices, solar panels and LEDs. One obstacle to mass production and widespread use of these wonder particles is the difficulty and expense associated with current chemical manufacturing methods that often requiring heat, high pressure and toxic solvents.

But now three Lehigh University engineers have successfully demonstrated the first precisely controlled, biological way to manufacture quantum dots using a single-enzyme, paving the way for a significantly quicker, cheaper and greener production method.

The Lehigh team— Bryan Berger, Class of 1961 Associate Professor, Chemical and Biomolecular Engineering; Chris Kiely, Harold B. Chambers Senior Professor, Materials Science and Engineering and Steven McIntosh, Class of 1961 Associate Professor, Chemical and Biomolecular Engineering, along with Ph.D. candidate Li Lu and undergraduate Robert Dunleavy—have detailed their findings in an article called “Single Enzyme Biomineralization of Cadmium Sulfide Nanocrystals with Controlled Optical Properties” published in theProceedings of the National Academy of Sciences.

“The beauty of a biological approach is that it cuts down on the production needs, environmental burden and production time quite a lot,” says Berger.

In July of last year, the team’s work was featured on the cover of Green Chemistry describing their use of “directed evolution” to alter a bacterial strain called Stenotophomonas maltophilia to selectively produce cadmium sulphide QDs. Because they discovered that a single enzyme produced by the bacteria is responsible for QD generation, the cell-based production route was scrapped entirely. The cadmium sulphide QDs, as they have now shown in the PNAS article, can be generated with the same enzyme synthesized from other easily engineered bacteria such as E. coli.

“We have evolved the enzyme beyond what nature intended,” says Berger, engineering it to not only make the crystal structure of the QDs, but control their size. The result is the ability to uniformly produce quantum dots that emit any particular color they choose—the very characteristic that makes this material attractive for many applications.

Industrial processes take many hours to grow the nanocrystals, which then need to undergo additional processing and purifying steps. Biosynthesis, on the other hand, takes minutes to a few hours maximum to make the full range of quantum dot sizes (about 2 to 3 nanometers) in a continuous, environmentally friendly process at ambient conditions in water that needs no post-processing steps to harvest the final, water-soluble product.

Perfecting the methodology to structurally analyze individual nanoparticles required a highly sophisticated Scanning Transmission Electron Microscope (STEM). Lehigh’s Electron Microscopy and Nanofabrication Facility was able to provide a $4.5 million state-of-the-art instrument that allowed the researchers to examine the structure and composition of each QD, which is only composed of tens to hundreds of atoms.

“Even with this new microscope, we’re pushing the limits of what can be done,” says Kiely.

The instrument scans an ultra-fine electron beam across a field of QDs. The atoms scatter the electrons in the beam, producing a kind of shadow image on a fluorescent screen, akin to the way an object blocking light produces a shadow on the wall. A digital camera records the highly magnified atomic resolution image of the nanocrystal for analysis.

The team is poised to scale-up its laboratory success into a manufacturing enterprise making inexpensive QDs in an eco-friendly manner. Conventional chemical manufacturing costs $1,000 to $10,000 per gram. A biomanufacturing technique could potentially slash the price by at least a factor of 10, and the team estimates yields on the order of grams per liter from each batch culture, says McIntosh.

Taking a long view, the three colleagues hope that their method will lead to a plethora of future QD applications, such as greener manufacturing of methanol, an eco-friendly fuel that could be used for cars, heating appliances and electricity generation. Water purification and metal recycling are two other possible uses for this technology.

“We want to create many different types of functional materials and make large-scale functional materials as well as individual quantum dots,” says McIntosh.

He imagines developing a process by which individual quantum dots arrange themselves into macrostructures, the way nature grows a mollusk shell out of individual inorganic nanoparticles or humans grow artificial tissue in a lab.

“If we’re able to make more of the material and control how it’s structured while maintaining its core functionality, we could potentially get a solar cell to assemble itself with .”

Explore further: Robust approach for preparing polymer-coated quantum dots

More information: Robert Dunleavy et al, Single-enzyme biomineralization of cadmium sulfide nanocrystals with controlled optical properties, Proceedings of the National Academy of Sciences (2016).DOI: 10.1073/pnas.1523633113

 

Supercritical Fluids Help Stabilize Quantum Dot Formation: Applications for Photoluminescent Materials; Bio-Imaging; Photonics and Optoelectronics


Supercritical QD ToyohashiTech-supercritical-CO2-quantum-dot-303705iufqusfpiufpqxa8Researchers have used supercritical CO2—CO2 at a temperature and pressure above the critical point such that distinctions between the liquid and gas phase do not exist—to stabilize the production of quantum dots (QDs). Their research has been published in The Journal of Supercritical Fluids and selected by the editor-in-chief as a featured article.
Semiconductor nanocrystals known as QDs are increasingly being used as photoluminescent materials in bio-imaging, photonics, and optoelectronic applications. In these applications, QDs must have stable photoluminescence properties, which is achieved by chemically modifying the surface of the QDs.
However, chemical modification of the surface typically requires large amounts of organic solvents that are harmful to the environment. To solve this problem, many researchers have attempted to synthesize polymer-nanoparticle composites by using supercritical fluid (SCF)-based technology. Supercritical CO2 has emerged as the most extensively studied SCF medium, because it is readily available, inexpensive, nonflammable, and environmentally benign.
Toyohashi Tech researchers, in cooperation with researchers at the National Institute of Technology, Kurume College, have investigated the formation of nanostructured material using supercritical CO2. They have demonstrated the formation of composite nanoparticles of luminescent ZnO QDs and polymers by dispersion polymerization in supercritical CO2. As a result of the supercritical-CO2-assisted surface modification of QDs, the QDs were well dispersed in the polymer matrix and showed high luminescence.
“Unfortunately, the photoluminescence properties of pristine luminescent QDs were quenched in supercritical CO2. The surface structure of the QDs was destroyed by supercritical CO2,” explained Associate Professor Kiyoshi Matsuyama from the National Institute of Technology, Kurume College.
“We found that the quenching of ZnO QDs could be prevented by coating with silica to obtain PMMA-ZnO composite QDs with high luminescence using a supercritical-CO2-assisted surface modification with polymer.”
The research shows that the supercritical-fluid-assisted process provides an environmentally benign route for producing stabilized luminescent materials.
The article can be found at: Matsuyama et al. (2015) Formation of Poly(Methyl Methacrylate)-ZnO Nanoparticle Quantum Dot Composites by Dispersion Polymerization in Supercritical CO2.