MIT researchers discover platform that manipulates organic molecules’ emission

qdot-images-3.jpgEnhancing and manipulating the light emission of organic molecules is at heart of many important technological and scientific advances, including in the fields of organic light emitting devices, bio-imaging, bio-molecular detection. Researchers at MIT have now discovered a new platform that enables dramatic manipulation of the emission of organic molecules when simply suspended on top of a carefully designed planar slab with a periodic array of holes: so-called photonic crystal surface.


Influenced by the fast and directional emission channels (called ‘resonances’) provided by the photonic crystal surface, molecules in the solution that are suspended on top of the surface no longer behave in their usual fashion: instead of sending light isotropically into all directions, they rather send light into specific directions.

The researchers say that this platform could also be applied to enhance other type of interactions of light with matter, such as Raman scattering. Furthermore, this process applies to any other nano-emitters as well, such as quantum dots.

Physics Professors Marin Soljacic and John Joannopoulos, Associate Professor of Applied Mathematics Steven Johnson, Research scientist Dr. Ofer Shapira, Postdocs Dr. Alejandro Rodriguez, Dr. Xiangdong Liang, and graduate students Bo Zhen, Song-Liang Chua, Jeongwon Lee report this discovery as featured in Proceedings of the National Academy of Sciences.

“Most fluorescing molecules are like faint light bulbs uniformly emitting light into all directions,” says Soljacic. Researchers have often sought to enhance this emission by incorporating organic emitters into sub-wavelength structured cavities that are usually made out of inorganic materials. However, the challenge lies in an inherent incompatibility in the fabrication of cavities for such hybrid systems.

Zhen et al present a simple and direct methodology to incorporate the organic emitters into their structures. By introducing a microfluidic channel on top of the photonic crystal surface, organic molecules in solution are delivered to the active region where interaction with light is enhanced. Each molecule then absorbs and emits significantly more energy with an emission pattern that can be designed to be highly directional. “Now we can turn molecules from being simple light bulbs to powerful flashlights that are thousands of times stronger and can all be aligned towards the same direction,” says Shapira, the senior author of the paper.

This discovery lends itself to a number of practical applications. “During normal blood tests, for example,” adds Shapira, “cells and proteins are labeled with antibodies and fluorescing molecules that allow their recognition and detection. Their detection limit could be significantly improved using such a system due to the enhanced directional emission from the molecules.”

The researchers also demonstrated that the directional emission can be turned into organic lasers with low input powers. “This lasing demonstration truly highlights the novelty of this system,” says the first author Zhen. For almost any lasing system to work there is a barrier on the input power level, named the lasing threshold, below which lasing will not happen. Naturally, the lower the threshold, the less power it takes to turn on this laser. Exploring the enhancement mechanisms present in the current platform, lasing was observed with a substantially lower barrier than before: the measured threshold in this new system is at least an order of magnitude lower than any previously reported results using the same molecules.

Source: Massachusetts Institute of Technology, Institute for Soldier Nanotechnologies

Guided growth of nanowires leads to self-integrated nanoelectronics circuits

QDOTS imagesCAKXSY1K 8(Nanowerk News) Researchers working with tiny  components in nanoelectronics face a challenge similar to that of parents of  small children: teaching them to manage on their own. The nano-components are so  small that arranging them with external tools is impossible. The only solution  is to create conditions in which they can be “trusted” to assemble themselves.
Much effort has gone into facilitating the self-assembly of  semiconductors, the basic building blocks of electronics, but until recently,  success has been limited. Scientists had developed methods for growing  semiconductor nanowires vertically on a surface, but the resultant structures  were short and disorganized. After growing, such nanowires need to be  “harvested” and aligned horizontally; since such placement is random, scientists  need to determine their location and only then integrate them into electric  circuits.
A team led by Prof. Ernesto Joselevich of the Weizmann  Institute’s Materials and Interfaces Department has managed to overcome these  limitations. For the first time, the scientists have created self-integrating  nanowires whose position, length and direction can be fully controlled.
This is a SEM image of a logic circuit based on 14 nanowires
This  is a SEM image of a logic circuit based on 14 nanowires.
The achievement, reported today in the Proceedings of the  National Academy of Sciences (“Self-integration of nanowires into circuits via  guided growth”), was based on a method developed by Joselevich two years ago  for growing nanowires horizontally in an orderly manner. In the present study —  conducted by Joselevich with Dr. Mark Schvartzman and David Tsivion of his lab,  and Olga Raslin and Dr. Diana Mahalu of the Physics of Condensed Matter  Department — the scientists went further, creating self-integrated electronic  circuits from the nanowires.
First, the scientists prepared a surface with tiny, atom-sized  grooves and then added to the middle of the grooves catalyst particles that  served as nuclei for the growth of nanowires. This setup defined the position,  length and direction of the nanowires. They then succeeded in creating a  transistor from each nanowire on the surface, producing hundreds of such  transistors simultaneously. The nanowires were also used to create a more  complex electronic component — a functioning logic circuit called an Address  Decoder, an essential constituent of computers. These ideas and findings have  earned Joselevich a prestigious European Research Council Advanced Grant.
“Our method makes it possible, for the first time, to determine  the arrangement of the nanowires in advance to suit the desired electronic  circuit,” Joselevich explains. The ability to efficiently produce circuits from  self-integrating semiconductors opens the door to a variety of technological  applications, including the development of improved LED devices, lasers and  solar cells.
Source: Weizmann Institute of Science 

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Why the Shape of Nanoparticles Matters

QDOTS imagesCAKXSY1K 8(Nanowerk News) Conventional treatments for diseases  such as cancer can carry harmful side effects—and the primary reason is that  such treatments are not targeted specifically to the cells of the body where  they’re needed. What if drugs for cancer, cardiovascular disease, and other  diseases can be targeted specifically and only to cells that need the medicine,  and leave normal tissues untouched?  
A new study involving Sanford-Burnham’s Erkki Ruoslahti, M.D.,  Ph.D., contributing to work by Samir Mitragotri, Ph.D., at the University of  California, Santa Barbara, found that the shape of nanoparticles can enhance  drug targeting. The study, published in Proceedings of the National Academy  of Sciences (“Using shape effects to target antibody-coated  nanoparticles to lung and brain endothelium”), found that rod-shaped  nanoparticles—or nanorods—as opposed to spherical nanoparticles, appear to  adhere more effectively to the surface of endothelial cells that line the inside  of blood vessels.
“While nanoparticle shape has been shown to impact cellular  uptake, the latest study shows that specific tissues can be targeted by  controlling the shape of nanoparticles. Keeping the material, volume, and the  targeting antibody the same, a simple change in the shape of the nanoparticle  enhances its ability to target specific tissues,” said Mitragotri.
“The elongated particles are more effective,” added Ruoslahti.  “Presumably the reason is that if you have a spherical particle and it has  binding sites on it, the curvature of the sphere allows only so many of those  binding sites to interact with membrane receptors on the surface of a cell.”
In contrast, the elongated nanorods have a larger surface area  that is in contact with the surface of the endothelial cells. More of the  antibodies that coat the nanorod can therefore bind receptors on the surface of  endothelial cells, and that leads to more effective cell adhesion and more  effective drug delivery.
Testing targeted nanoparticles
Mitragotri’s lab tested the efficacy of  rod-shaped nanoparticles in synthesized networks of channels called “synthetic  microvascular networks,” or SMNs, that mimic conditions inside blood vessels.  The nanoparticles were also tested in vivo in animal models, and separately in  mathematical models.
The researchers also found that nanorods targeted to lung tissue  in mice accumulated at a rate that was two-fold over nanospheres engineered with  the same targeting antibody. Also, enhanced targeting of nanorods was seen in  endothelial cells in the brain, which has historically been a challenging organ  to target with drugs.
Nanoparticles already used in some cancer drugs
Nanoparticles have been studied as vessels to carry drugs  through the body. Once they are engineered with antibodies that bind to specific  receptors on the surface of targeted cells, these nanoparticles also can, in  principle, become highly specific to the disease they are designed to treat.
Ruoslahti, a pioneer in the field of cell adhesion—how cells  bind to their surroundings—has developed small chain molecules called peptides  that can be used to target drugs to tumors and atherosclerotic plaques.
Promising results
“Greater specific attachment exhibited by rod-shaped particles  offers several advantages in the field of drug delivery, particularly in the  delivery of drugs such as chemotherapeutics, which are highly toxic and  necessitate the use of targeted approaches,” the authors wrote in their paper.
The studies demonstrate that nanorods with a high aspect ratio  attach more effectively to targeted cells compared with spherical nanoparticles.  The findings hold promise for the development of novel targeted therapies with  fewer harmful side effects.
Source: Sanford-Burnham Medical Research Institute 

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Researchers can deliver RNA, proteins and nanoparticles for many applications

QDOTS imagesCAKXSY1K 8How to squeeze large molecules into cells

By deforming cells, researchers can deliver RNA, proteins and nanoparticles for many applications
January 28, 2013

As cells squeeze through a narrow channel, tiny holes open in their membranes, allowing large molecules such as RNA to pass through (credit: Armon Sharei and Emily Jackson)

Living cells are surrounded by a membrane that tightly regulates what gets in and out of the cell. This barrier is necessary for cells to control their internal environment, but it makes it more difficult for scientists to deliver large molecules such as nanoparticles for imaging, or proteins that can reprogram them into pluripotent stem cells.squeezed_cells

Researchers from MIT have now found a safe and efficient way to get large molecules through the cell membrane, by squeezing the cells through a narrow constriction that opens up tiny, temporary holes in the membrane. Any large molecules floating outside the cell — such as RNA, proteins or nanoparticles — can slide through the membrane during this disruption.

Using this technique, the researchers were able to deliver reprogramming proteins and generate induced pluripotent stem cells with a success rate 10 to 100 times better than any existing method. They also used it to deliver nanoparticles, including carbon nanotubes and quantum dots, which can be used to image cells and monitor what’s happening inside them.

“It’s very useful to be able to get large molecules into cells. We thought it might be interesting if you could have a relatively simple system that could deliver many different compounds,” says Klavs Jensen, the Warren K. Lewis Professor of Chemical Engineering, professor of materials science and engineering, and a senior author of a paper describing the new device in the Proceedings of the National Academy of Sciences.

Robert Langer, the David H. Koch Institute Professor at MIT, is also a senior author of the paper. Lead authors are chemical engineering graduate student Armon Sharei, Koch Institute research scientist Janet Zoldan, and chemical engineering research associate Andrea Adamo.

The new MIT system appears to work for many cell types — so far, the researchers have successfully tested it with more than a dozen types, including both human and mouse cells. It also works in cells taken directly from human patients, which are usually much more difficult to manipulate than human cell lines grown specifically for lab research.

The new device builds on previous work by Jensen and Langer’s labs, in which they used microinjection to force large molecules into cells as they flowed through a microfluidic device. This wasn’t as fast as the researchers would have liked, but during these studies, they discovered that when a cell is squeezed through a narrow tube, small holes open in the cell membrane, allowing nearby molecules to diffuse into the cell.

To take advantage of that, the researchers built rectangular microfluidic chips, about the size of a quarter, with 40 to 70 parallel channels. Cells are suspended in a solution with the material to be delivered and flowed through the channel at high speed — about one meter per second. Halfway through the channel, the cells pass through a constriction about 30 to 80 percent smaller than the cells’ diameter. The cells don’t suffer any irreparable damage, and they maintain their normal functions after the treatment.

Special delivery

The research team is now further pursuing stem cell manipulation, which holds promise for treating a wide range of diseases. They have already shown that they can transform human fibroblast cells into pluripotent stem cells, and now plan to start working on delivering the proteins needed to differentiate stem cells into specialized tissues.

Another promising application is delivering quantum dots — nanoparticles made of semiconducting metals that fluoresce. These dots hold promise for labeling individual proteins or other molecules inside cells, but scientists have had trouble getting them through the cell membrane without getting trapped in endosomes.

In a paper published in November, working with MIT graduate student Jungmin Lee and chemistry professor Moungi Bawendi, the researchers showed that they could get quantum dots inside human cells grown in the lab, without the particles becoming confined in endosomes or clumping together. They are now working on getting the dots to tag specific proteins inside the cells.

The researchers are also exploring the possibility of using the new system for vaccination. In theory, scientists could remove immune cells from a patient, run them through the microfluidic device and expose them to a viral protein, and then put them back in the patient. Once inside, the cells could provoke an immune response that would confer immunity against the target viral protein.

The research was funded by the National Institutes of Health and the National Cancer Institute.

Flexible Electronics Help Create Multi Sensing Cardiac Ablation Catheter

by GENE OSTROVSKY on Nov 16, 2012

flexible cardiac ablation catheter Flexible Electronics Help Create Multi Sensing Cardiac Ablation CatheterFlexible electronics are a fairly new advancement with the promise of radically transforming certain aspects of medicine. Unlike many technologies that take years to reach practical implementation, flexible electronics are already being embedded to significantly improve the functionality of existing devices. As an early example that was just announced, an international team of researchers built and tested a balloon ablation catheter capable of measuring intracardiac pressure, EKG, and local temperature around the device tip. All this data can be monitored in real time by the physician during ablation without having to switch devices.

The technology behind the flexible electronics is being developed by MC10, a company we’ve been following for the last couple of years as they rush to bring new capabilities to medical devices.

From Northwestern University:

Central to the design is a section of catheter that is printed with a thin layer of stretchable electronics. The catheter’s exterior protects the electronics during its trip through the bloodstream; once inside the heart, the catheter is inflated like a balloon, exposing the electronics to a larger surface area inside the heart.

With the catheter is in place, the individual devices within can perform their specific tasks. A pressure sensor determines the pressure on the heart; an EKG sensor monitors the heart’s condition during the procedure; and a temperature sensor controls the temperature so as not to damage surrounding tissue. The temperature can also be controlled during the procedure without removing the catheter.

These devices can deliver critical, high-quality information — such as temperature, mechanical force, and blood flow — to the surgeon in real time, and the system is designed to operate reliably without any changes in properties as the balloon inflates and deflates.

Flexible electronics flashbacks on Medgadget

Northwesten press release: Simplifying Heart Surgery with Stretchable Electronic Devices

More from MC10: MC10′s Latest Research on Cardiac Webs and Instrumented Catheters in the Proceedings of the National Academy of Sciences (PNAS)

Study abstract in PNASElectronic sensor and actuator webs for large-area complex geometry cardiac mapping and therapy