I was kind of shocked and amazed by a recent publication in NanoLetters. It seems that viscosity measurements are still difficult. In my ignorance, I had assumed that this was a solved problem. And, just to show the depths of my ignorance, it turns out that you can learn something about a person's health by measuring the viscosity of their blood. This process is time consuming, as I'll explain in a moment. Now, thanks to the power of our ability to build little gold-iron alloy helices, these measurements just got a whole lot easier.

Stick around and I'll tell you about viscosity

Viscosity is a measure of how well things flow. So, for instance, water flows quite easily and rapidly, while some oils flow more slowly—we say that oil is more viscous than water. The study of fluid flow is a very complicated business so, to simplify the problem, you have to ask yourself what is important. For instance, water flowing down a river is probably dominated by the sheer mass of moving fluid. That means you can probably ignore any influence of viscosity and just worry about mass.

On the other hand, when blood reaches the extremities of the body, it is flowing in very fine channels. There is not a lot of mass to the fluid, but the viscous forces between the channel wall and the fluid are enormous. Here, it might be appropriate to ignore anything to do with mass and focus on viscosity. By examining relationships like this, you can build reasonably accurate models of fluid flows without enduring the pain of the full complexity of fluid dynamics equations. But you can only choose what to include in your models if you know the viscosity reasonably accurately.

Sorry, I don't see the trouble

Given this back story, you might think that viscosity is relatively simple to measure: track how fast an object moves through a fluid, or the volume flow of a liquid through a capillary, or something like that. And, traditionally, there are many variations on these themes that provide you numbers that represent the viscosity of a fluid.

But that's not the whole story. Take blood, for instance. Blood consists of water with a lot of other small molecules and larger proteins. But it's also filled with larger objects, like red and white blood cells. At the macroscopic level, the cells dominate the viscous properties of the fluid; at small scales, which are the scales that matter for flow through a capillary, the fluid matters.

So, according to researchers, it is really important to measure the viscosity of the fluid and not the viscosity of the fluid and blood cells. That, at present, is done by separating blood into its component parts and measuring the viscosity of the blood plasma. However, it would be nice to eliminate the separation step, especially if you need the result fast. (To be honest, I have no idea if blood viscosity measurements would help in any situation where speed was critical... Physicist, remember?)

Let me put a little gold in your blood

The basic idea behind the new work is to measure the viscosity of the fluid between the blood cells, which requires a probe that is much smaller than the cells themselves. Enter plasmonic antennas. Plasmonic antennas are little dollops of metal, somewhere between 20 and 200nm (10-9m) in size. These metallic blobs respond fiercely to light.

This response depends on them being metal. The reason a metal is reflective is that its electrons are free to move around in response to light. When a light field hits the metal, the electrons re-radiate its electric field by jiggling up and down in response. Normally, this behavior is averaged out over any substantial hunk of metal.

If the metal is just a tiny blob, then the electrons are restricted in their motion: they pile up at one end of the blob and slosh back to the other. In doing so, they create an enormous electric field, so they radiate lots of light in every direction. As a result, little gold particles scatter huge amounts of light.

(Incidentally, you can see this in Roman glassware, where scattering of green light on gold particles that are embedded in the glass give the glass its characteristic green color in reflection. But, when you hold the glass up to the light, it appears red, because red light is transmitted.)

This strong and specific response makes plasmonic antennas and a bit of light a very useful tool for probing very tiny volumes. Except in blood, where you can't track any light radiated by the antenna. Even if red blood cells were transparent, blood would be opaque. The cells in blood scatter a lot of light, so you cannot track the origin of a light source.

Look at it this way: you want to track a plasmonic antenna as it drifts through the blood. You shine light on the fluid, and the antenna responds to the light, glowing brightly. But that glow is diffused by scattering off the surrounding cells, making it impossible to pin down. Experimental failure is coming your way.

Building a spiral

And this is where the researchers got clever. Instead of making gold spheres or bars, the researchers made tiny spirals that were just 170nm long and 50nm wide. These antennas will scatter light, too. But their response is strongly dependent on the polarization of the light.

Imagine that you are sitting facing an incoming beam of light. As the light approaches, the electric field will oscillate, but the oscillation can take many forms. For instance it might grow sideways to your left and then collapse to nothing before growing sideways to the right and collapsing to repeat the pattern. It could do the same, but in a vertical direction.

These are linear polarizations. However, the electric field might not do any of that. Instead, the size of the electric field might remain the same, but the direction it is oriented rotates either clockwise or counterclockwise. In this form, called circularly polarized light, it looks like a corkscrew coming to extract you from your front row seat.



Further Reading Polarization

When the wavelength of light for this circular polarization matches the pitch of the helix, the helix will scatter very strongly. But it will only respond if two conditions are met. The direction of the helix and the direction of rotation of the circularly polarized light have to match. And, the helix needs to meet the light head on. If you send in light that is a mixture of the two circular polarizations, one polarization scatters back very strongly and the other does not. This can be measured and used to determine the orientation of the antenna relative to the direction the light was traveling. And, the difference in scattering for the different polarization is not very strongly influenced by the cells floating around in the blood.

The helical shape gives the researchers a signal that is unique to their antenna, and it depends on the alignment of the particle relative to the incoming light. So it necessarily tells you something about the antenna's location.

Inspiration does strike the same place twice

The second innovation was not to use gold. Usually, researchers use gold because it is the best material for supporting plasmons. Instead, the researchers used an alloy of gold and iron. Iron is a really poor plasmonic material, but it is an excellent magnetic material. The researchers sacrificed some plasmonic response to gain a material that also responds to a magnetic field.

The idea is that, thanks to the shape of the antenna, applying a magnetic field causes the helix to align along the direction of the magnetic field. At this point, you may be able to see what is coming: this is a plasmonic antenna that gives a unique signal that depends on its orientation relative to the light. And that orientation can be controlled.

A viscosity measurement is made by rotating the magnetic field. The antennas will respond, continuously lining up to the magnetic field. But, thanks to the drag due to the fluid's viscosity, they will always lag slightly. Measuring the lag allows the viscosity to be calculated.

And that is exactly what the researchers did. They showed that they could measure viscosity in various sugar-water combinations, sugar-water with beads, and finally with reconstituted blood (with varying fractions of blood cells). In the case of the sugar-water mixtures, they showed that they get numbers that are comparable with traditional measurements.

But traditional measurements of reconstituted blood, and sugar-water with beads showed a much higher viscosity. This is because the traditional measurements are dominated by the presence of the beads and cells. The nano antennas, on the other hand, gave results that were more in line with measurements made on the fluid without the beads or cells. This showed that it was possible to measure the viscosity without separating the blood into plasma and cellular material.

What's more, the researchers showed that they were doing this under circumstances where an ordinary light scattering measurement was impossible: the fluids were opaque when mixed with beads or blood cells. Nevertheless, by using the polarization-sensitive response of the helix antennas, they were able to pick out the signal and make effective measurements. That is quite remarkable.

Where to now

First off, I should say that I have no idea if measuring blood viscosity is as important as the researchers make it out to be. I should also say that there is work to be done on the precision of the measurement. At the moment, they show that it works, but the error bars are too large to be clinically useful, I suspect. However, this is a first attempt, and a very clever idea, so I think we can expect some improvement.

NanoLetters, 2016, DOI: 10.1021/acs.nanolett.6b01404