Tag Archives: St. Paul’s Cathedral

Nanoparticle detection with whispers and bubbles

Caption: A magnified photograph of a glass Whispering Gallery Resonator. The bubble is extremely small, less than the width of a human hair. Credit: OIST (Okinawa Institute of Science and Technology Graduate University)

It was the reference to a whispering gallery which attracted my attention; a July 11, 2018 news item on Nanowerk is where I found it,

Technology created by researchers at the Okinawa Institute of Science and Technology Graduate University (OIST) [Japan] is literally shedding light on some of the smallest particles to detect their presence – and it’s made from tiny glass bubbles.

The technology has its roots in a peculiar physical phenomenon known as the “whispering gallery,” described by physicist Lord Rayleigh (John William Strutt) in 1878 and named after an acoustic effect inside the dome of St Paul’s Cathedral in London. Whispers made at one side of the circular gallery could be heard clearly at the opposite side. It happens because sound waves travel along the walls of the dome to the other side, and this effect can be replicated by light in a tiny glass sphere just a hair’s breadth wide called a Whispering Gallery Resonator (WGR).

A July 11, 2018 OIST press release by Andrew Scott (also on EurekAlert), provides more details,

When light is shined into the sphere, it bounces around and around the inner surface, creating an optical carousel. Photons bouncing along the interior of the tiny sphere can end up travelling for long distances, sometimes as far as 100 meters. But each time a photon bounces off the sphere’s surface, a small amount of light escapes. This leaking light creates a sort of aura around the sphere, known as an evanescent light field. When nanoparticles come within range of this field, they distort its wavelength, effectively changing its color. Monitoring these color changes allows scientists to use the WGRs as a sensor; previous research groups have used them to detect individual virus particles in solution, for example. But at OIST’s Light-Matter Interactions Unit, scientists saw they could improve on previous work and create even more sensitive designs. The study is published in Optica.

Today, Dr. Jonathan Ward is using WGRs to detect minute particles more efficiently than ever before. The WGRs they have made are hollow glass bubbles rather than balls, explains Dr. Ward. “We heated a small glass tube with a laser and had air blown down it – it’s a lot like traditional glass blowing”. Blowing the air down the heated glass tube creates a spherical chamber that can support the sensitive light field. The most noticeable difference between a blown glass ornament and these precision instruments is the scale: the glass bubbles can be as small as 100 microns- a fraction of a millimeter in width. Their size makes them fragile to handle, but also malleable.

Working from theoretical models, Dr. Ward showed that they could increase the size of the light field by using a thin spherical shell (a bubble, in other words) instead of a solid sphere. A bigger field would increase the range in which particles can be detected, increasing the efficacy of the sensor. “We knew we had the techniques and the materials to fabricate the resonator”, said Dr. Ward. “Next we had to demonstrate that it could outperform the current types used for particle detection”.

To prove their concept, the team came up with a relatively simple test. The new bubble design was filled with a liquid solution containing tiny particles of polystyrene, and light was shined along a glass filament to generate a light field in its liquid interior. As particles passed within range of the light field, they produced noticeable shifts in the wavelength that were much more pronounced than those seen with a standard spherical WGR.

With a more effective tool now at their disposal, the next challenge for the team is to find applications for it. Learning what changes different materials make to the light field would allow Dr Ward to identify and target them, and even control their activity.

Despite their fragility, these new versions of WGRs are easy to manufacture and can be safely transported in custom made cases. That means these sensors could be used in a wide verity of fields, such as testing for toxic molecules in water to detect pollution, or detecting blood borne viruses in extremely rural areas where healthcare may be limited.

For Dr. Ward however, there’s always room from improvement: “We’re always pushing to get even more sensitivity and find the smallest particle this sensor can detect. We want to push our detection to the physical limits.”

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

Nanoparticle sensing beyond evanescent field interaction with a quasi-droplet microcavity by Jonathan M. Ward, Yong Yang, Fuchuan Lei, Xiao-Chong Yu, Yun-Feng Xiao, and Síle Nic Chormaic. Optica Vol. 5, Issue 6, pp. 674-677 (2018) https://doi.org/10.1364/OPTICA.5.000674

This paper is open access.

How many Holy Grails are there? Nanoscientists have reached another one (cancer, again)

A July 24, 2013 news item on ScienceDaily mentions the latest ‘Holy Grail’ breakthrough’,

Just months after setting a record for detecting the smallest single virus in solution, researchers at the Polytechnic Institute of New York University (NYU-Poly) have announced a new breakthrough: They used a nano-enhanced version of their patented microcavity biosensor to detect a single cancer marker protein, which is one-sixth the size of the smallest virus, and even smaller molecules below the mass of all known markers.

The July 24, 2013 Polytechnic Institute of New York University (NYU-Poly) press release features the Holy Grail in its headline (Note: Links have been removed),

NYU-Poly Nano Scientists Reach the Holy Grail in Label-Free Cancer Marker Detection: Single Molecules

Unlike current technology, which attaches a fluorescent molecule, or label, to the antigen to allow it to be seen, the new process detects the antigen without an interfering label.
Stephen Arnold, university professor of applied physics and member of the Othmer-Jacobs Department of Chemical and Biomolecular Engineering, published details of the achievement in Nano Letters, a publication of the American Chemical Society.

The press release goes on to the describe the context for this breakthrough and provides details about it (Note: A link has been removed),

In 2012, Arnold and his team were able to detect in solution the smallest known RNA virus, MS2, with a mass of 6 attograms. Now, with experimental work by postdoctoral fellow Venkata Dantham and former student David Keng, two proteins have been detected: a human cancer marker protein called Thyroglobulin, with a mass of just 1 attogram, and the bovine form of a common plasma protein, serum albumin, with a far smaller mass of 0.11 attogram. [emphasis mine] “An attogram is a millionth of a millionth of a millionth of a gram,” said Arnold, “and we believe that our new limit of detection may be smaller than 0.01 attogram.”

This latest milestone builds on a technique pioneered by Arnold and collaborators from NYU-Poly and Fordham University.  In 2012, the researchers set the first sizing record by treating a novel biosensor with plasmonic gold nano-receptors, enhancing the electric field of the sensor and allowing even the smallest shifts in resonant frequency to be detected. Their plan was to design a medical diagnostic device capable of identifying a single virus particle in a point-of-care setting, without the use of special assay preparations.

At the time, the notion of detecting a single protein—phenomenally smaller than a virus—was set forth as the ultimate goal.

“Proteins run the body,” explained Arnold. “When the immune system encounters virus, it pumps out huge quantities of antibody proteins, and all cancers generate protein markers. A test capable of detecting a single protein would be the most sensitive diagnostic test imaginable.”

To the surprise of the researchers, examination of their nanoreceptor under a transmission electron microscope revealed that its gold shell surface was covered with random bumps roughly the size of a protein. Computer mapping and simulations created by Stephen Holler, once Arnold’s student and now assistant professor of physics at Fordham University, showed that these irregularities generate their own highly reactive local sensitivity field extending out several nanometers, amplifying the capabilities of the sensor far beyond original predictions. “A virus is far too large to be aided in detection by this field,” Arnold said. “Proteins are just a few nanometers across—exactly the right size to register in this space.”

The implications of single protein detection are significant and may lay the foundation for improved medical therapeutics.  Among other advances, Arnold and his colleagues posit that the ability to follow a signal in real time—to actually witness the detection of a single disease marker protein and track its movement—may yield new understanding of how proteins attach to antibodies.

Arnold named the novel method of label-free detection “whispering gallery-mode biosensing” because light waves in the system reminded him of the way that voices bounce around the whispering gallery under the dome of St. Paul’s Cathedral in London. A laser sends light through a glass fiber to a detector. When a microsphere is placed against the fiber, certain wavelengths of light detour into the sphere and bounce around inside, creating a dip in the light that the detector receives. When a molecule like a cancer marker clings to a gold nanoshell attached to the microsphere, the microsphere’s resonant frequency shifts by a measureable amount.

Just a brief comment about the attogram, this is the first time I’ve seen atto prepended to anything other than a unit of time, e.g. attosecond. For anyone who’s not familiar with the atto scale, it’s less than femto,which is less than pico, which is less than nano. There are two more scales moving downward after atto:  zetto followed by yocto. As far as I’m aware, yocto is still the smallest unit of measurement. (more simply and moving down in scale: micro, nano, pico, femto, atto, zetto, yocto)

Back to the Holy Grail at hand, here’s a link to and a citation for the published paper,

Label-Free Detection of Single Protein Using a Nanoplasmonic-Photonic Hybrid Microcavity by Venkata R. Dantham, Stephen Holler, Curtis Barbre, David Keng, Vasily Kolchenko, and Stephen Arnold. Nano Lett., 2013, 13 (7), pp 3347–3351 DOI: 10.1021/nl401633y Publication Date (Web): June 18, 2013
Copyright © 2013 American Chemical Society

This paper is behind a paywall.