Tag Archives: cancer diagnosis

Probing the physical limits of plasmons in organic molecules with fewer than 50 atoms

A Sept. 5, 2018  news item on ScienceDaily introduces the work,

Rice University [Texas, US] researchers are probing the physical limits of excited electronic states called plasmons by studying them in organic molecules with fewer than 50 atoms.

A Sept. 4, 2018 Rice University news release (also on EurekAlert published on Sept. 5, 2018), which originated the news item, explains what plasmons are and why this research is being undertaken,

Plasmons are oscillations in the plasma of free electrons that constantly swirl across the surface of conductive materials like metals. In some nanomaterials, a specific color of light can resonate with the plasma and cause the electrons inside it to lose their individual identities and move as one, in rhythmic waves. Rice’s Laboratory for Nanophotonics (LANP) has pioneered a growing list of plasmonic technologies for applications as diverse as color-changing glass, molecular sensing, cancer diagnosis and treatment, optoelectronics, solar energy collection and photocatalysis.

Reporting online in the Proceedings of the National Academy of Sciences, LANP scientists detailed the results of a two-year experimental and theoretical study of plasmons in three different polycyclic aromatic hydrocarbons (PAHs). Unlike the plasmons in relatively large metal nanoparticles, which can typically be described with classical electromagnetic theory like Maxwell’s [James Clerk Maxwell] equations, the paucity of atoms in the PAHs produces plasmons that can only be understood in terms of quantum mechanics, said study co-author and co-designer Naomi Halas, the director of LANP and the lead researcher on the project.

“These PAHs are essentially scraps of graphene that contain five or six fused benzene rings surrounded by a perimeter of hydrogen atoms,” Halas said. “There are so few atoms in each that adding or removing even a single electron dramatically changes their electronic behavior.”

Halas’ team had experimentally verified the existence of molecular plasmons in several previous studies. But an investigation that combined side by side theoretical and experimental perspectives was needed, said study co-author Luca Bursi, a postdoctoral research associate and theoretical physicist in the research group of study co-designer and co-author Peter Nordlander.

“Molecular excitations are a ubiquity in nature and very well studied, especially for neutral PAHs, which have been considered as the standard of non-plasmonic excitations in the past,” Bursi said. “Given how much is already known about PAHs, they were an ideal choice for further investigation of the properties of plasmonic excitations in systems as small as actual molecules, which represent a frontier of plasmonics.”

Lead co-author Kyle Chapkin, a Ph.D. student in applied physics in the Halas research group, said, “Molecular plasmonics is a new area at the interface between plasmonics and molecular chemistry, which is rapidly evolving. When plasmonics reach the molecular scale, we lose any sharp distinction of what constitutes a plasmon and what doesn’t. We need to find a new rationale to explain this regime, which was one of the main motivations for this study.”

In their native state, the PAHs that were studied — anthanthrene, benzo[ghi]perylene and perylene — are charge-neutral and cannot be excited into a plasmonic state by the visible wavelengths of light used in Chapkin’s experiments. In their anionic form, the molecules contain an additional electron, which alters their “ground state” and makes them plasmonically active in the visible spectrum. By exciting both the native and anionic forms of the molecules and comparing precisely how they behaved as they relaxed back to their ground states, Chapkin and Bursi built a solid case that the anionic forms do support molecular plasmons in the visible spectrum.

The key, Chapkin said, was identifying a number of similarities between the behavior of known plasmonic particles and the anionic PAHs. By matching both the timescales and modes for relaxation behaviors, the LANP team built up a picture of a characteristic dynamics of low-energy plasmonic excitations in the anionic PAHs.

“In molecules, all excitations are molecular excitations, but select excited states show some characteristics that allow us to draw a parallel with the well-established plasmonic excitations in metal nanostructures,” Bursi said.

“This study offers a window on the sometimes surprising behavior of collective excitations in few-atom quantum systems,” Halas said. “What we’ve learned here will aid our lab and others in developing quantum-plasmonic approaches for ultrafast color-changing glass, molecular-scale optoelectronics and nonlinear plasmon-mediated optics.”

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

Lifetime dynamics of plasmons in the few-atom limit by Kyle D. Chapkin, Luca Bursi, Grant J. Stec, Adam Lauchner, Nathaniel J. Hogan, Yao Cui, Peter Nordlander, and Naomi J. Halas. PNAS September 11, 2018 115 (37) 9134-9139; published ahead of print August 27, 2018 DOI: https://doi.org/10.1073/pnas.1805357115

This paper is behind a paywall.

Attomolar cancer detection: measuring microRNAs in blood

The latest research does not lead to a magical disease detector where nanoscale sensors swim through the body continuously monitoring our health and alerting us should something untoward occur (see this Oct. 28, 2014 article on RT.com for more about Google X’s development plans for it and this Nov. 11, 2015 news item on Nanowerk for a measured response from a researcher in the field).

Now onto some real research, a Nov. 17, 2015 news item on ScienceDaily announces an ultrasensitive (attoscale) sensor employing gold nanoparticles for detecting cancer,

A simple, ultrasensitive microRNA sensor developed and tested by researchers from the schools of science and medicine at Indiana University-Purdue University Indianapolis and the Indiana University Melvin and Bren Simon Cancer Center holds promise for the design of new diagnostic strategies and, potentially, for the prognosis and treatment of pancreatic and other cancers.

A Nov. 17, 2015 Indiana University-Purdue University Indianapolis news release on EurekAlert, which originated the news item, provides more detail about research that seems to have focused largely on pancreatic cancer detection (Note: Links have been removed),

In a study published in the Nov. [2015] issue of ACS Nano, a peer-reviewed journal of the American Chemical Society focusing on nanoscience and nanotechnology research, the IUPUI researchers describe their design of the novel, low-cost, nanotechnology-enabled reusable sensor. They also report on the promising results of tests of the sensor’s ability to identify pancreatic cancer or indicate the existence of a benign condition by quantifying changes in levels of microRNA signatures linked to pancreatic cancer. MicroRNAs are small molecules of RNA that regulate how larger RNA molecules lead to protein expression. As such, microRNAs are very important in biology and disease states.

“We used the fundamental concepts of nanotechnology to design the sensor to detect and quantify biomolecules at very low concentrations,” said Rajesh Sardar, Ph.D., who developed the sensor.

“We have designed an ultrasensitive technique so that we can see minute changes in microRNA concentrations in a patient’s blood and confirm the presence of pancreatic cancer.” Sardar is an assistant professor of chemistry and chemical biology in the School of Science at IUPUI and leads an interdisciplinary research program focusing on the intersection of analytical chemistry and the nanoscience of metallic nanoparticles.

“If we can establish that there is cancer in the pancreas because the sensor detects high levels of microRNA-10b or one of the other microRNAs associated with that specific cancer, we may be able to treat it sooner,” said Murray Korc, M.D., the Myles Brand Professor of Cancer Research at the IU School of Medicine and a researcher at the IU Simon Cancer Center. Korc, worked with Sardar to improve the sensor’s capabilities and led the testing of the sensor and its clinical uses as well as advancing the understanding of pancreatic cancer biology.

“That’s especially significant for pancreatic cancer, because for many patients it is symptom-free for years or even a decade or more, by which time it has spread to other organs, when surgical removal is no longer possible and therapeutic options are limited,” said Korc. “For example, diagnosis of pancreatic cancer at an early stage of the disease followed by surgical removal is associated with a 40 percent five-year survival. Diagnosis of metastatic pancreatic cancer, by contrast, is associated with life expectancy that is often only a year or less.

“The beauty of the sensor designed by Dr. Sardar is its ability to accurately detect mild increases in microRNA levels, which could allow for early cancer diagnosis,” Korc added.

Over the past decade, studies have shown that microRNAs play important roles in cancer and other diseases, such as diabetes and cardiovascular disorders. The new IUPUI nanotechnology-based sensor can detect changes in any of these microRNAs.

The sensor is a small glass chip that contains triangular-shaped gold nanoparticles called ‘nanoprisms.’ After dipping it in a sample of blood or another body fluid, the scientist measures the change in the nanoprism’s optical property to determine the levels of specific microRNAs.

For anyone concerned about the cost associated with creating sensors based on gold, about patents, or about current techniques for monitoring microRNAs, there’s more from the news release (Note: A link has been removed),

“Using gold nanoprisms may sound expensive, but it isn’t because these particles are so very tiny,” Sardar said. “It’s a rather cheap technique because it uses nanotechnology and needs very little gold. $250 worth of gold makes 4,000 sensors. Four thousand sensors allow you to do at least 4,000 tests. The low cost makes this technique ideal for use anywhere, including in low-resource environments in this country and around the world.”

Indiana University Research and Technology Corporation has filed a patent application on Sardar’s and Korc’s groundbreaking nanotechnology-enabled sensor. The researchers’ ultimate goal is to design ultrasensitive and extremely selective low-cost point-of-care diagnostics enabling individual therapeutic approaches to diseases.

Currently, polymerase chain reaction technology is used to determine microRNA signatures, which requires extraction of the microRNA from blood or other biological fluid and reverse transcription or amplification of the microRNA. PCR provides relative values. By contrast, the process developed at IUPUI is simpler, quantitative, more sensitive and highly specific even when two different microRNAs vary in a single position. The study demonstrated that the IUPUI nanotechnology-enabled sensor is as good as if not better than the most advanced PCR in detection and quantification of microRNA.

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

Label-Free Nanoplasmonic-Based Short Noncoding RNA Sensing at Attomolar Concentrations Allows for Quantitative and Highly Specific Assay of MicroRNA-10b in Biological Fluids and Circulating Exosomes by Gayatri K. Joshi, Samantha Deitz-McElyea, Thakshila Liyanage, Katie Lawrence, Sonali Mali, Rajesh Sardar*, and Murray Korc. ACS Nano, Article ASAP DOI: 10.1021/acsnano.5b04527 Publication Date (Web): October 7, 2015

Copyright © 2015 American Chemical Society

This is an open access paper.

The researchers have provided this illustration of gold nanoprisms,

Caption: Indiana University-Purdue University Indianapolis researchers have developed a novel, low-cost, nanotechnology-enabled reusable sensor for which a patent application has been filed. Credit: Department of Chemistry and Chemical Biology, School of Science, Indiana University-Purdue University Indianapolis

Caption: Indiana University-Purdue University Indianapolis researchers have developed a novel, low-cost, nanotechnology-enabled reusable sensor for which a patent application has been filed. Credit: Department of Chemistry and Chemical Biology, School of Science, Indiana University-Purdue University Indianapolis

Bees and smart bombs

I wasn’t expecting to think about bees and bombs again (after my July 28, 2010 posting on science knitting and yarn bombing respectively) but then this news item, Novel bee venom derivative forms a nanoparticle ‘smart bomb’ to target cancer cells, popped up on Nanowerk last week. From the news item,

The next time you are stung by a bee, here’s some consolation: a toxic protein in bee venom, when altered, significantly improves the effectiveness liposome-encapsulated drugs or dyes, such as those already used to treat or diagnose cancer. This research [Samuel Wickline], described in the August 2010 print issue of the FASEB [Federation of American Societies for Experimental Biology] Journal, shows how modified melittin may revolutionize treatments for cancer and perhaps other conditions, such as arthritis, cardiovascular disease, and serious infections.

I gather the joournal’s editor is also experiencing these coincidences,

“Our journal is abuzz in a hive of bee-related discoveries. Just last month, we published research showing for the first time how honey kills bacteria. This month, the Wickline study shows how bee venom peptides can form “smart bombs” that deliver liposomal nanoparticles directly to their target, without collateral damage,” said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal.

That’s a lot of military jargon.