Hide and Seek

May 29, 2008 by Grant Drenkow

Remember the game hide and seek?  If you played this game outside, as a “hider” it was important to find a really big tree so the “seeker” had no chance of spotting you.  As the seeker, you always wondered if anyone was hiding behind the big trees. 

The same thing happens in the world of particle analysis.   The particle analyzers can very easily spot the big particles and measure their size.  However, you always wonder if a small particle is hiding behind the large one? 

Not any more!  You might want to check out this application note.  The advantage in hide and seek now goes to the seeker with a new technological breakthrough in particle analysis.  I’m not going to shamelessly hype any products but you should probably at least take a look at this new technology. 

Application Note is found at:  http://www.chem.agilent.com/temp/radF9367/00001916.PDF

Product information at: http://www.chem.agilent.com/Scripts/PDS.asp?lPage=62634

Chocolate Milk

May 9, 2008 by Grant Drenkow

I remember as a kid we were sometimes allowed to mix up a glass of chocolate milk after school.  If we used too much of the chocolate powder or we didn’t mix it properly, we ended up with a bunch of black goo in the bottom of the glass.   And yet when we had the little containers of chocolate milk at school, it didn’t have that problem.  Why was that?

Chocolate milk reminds me a little of particle analysis and the zeta potential of colloids.  Agilent has recently introduced its Series 7000 line of particle analyzers.  (See www.agilent.com/chem/particles for more info) One of the analyzers - the Agilent ZetaProbe - is all about ensuring the stability of the suspension.  As I talk with customers working with colloids not everyone understands the power of using zeta potential to ensure the stability of the suspension. 

If you’re someone dealing with suspensions, let me recommend a couple of resources to learn more about zeta potential.  

Applications notes explaining zeta potential: http://www.chem.agilent.com/scripts/LiteratureResults.asp?iprodinfotype=4&imodel=1765 

e-seminar presentation given by Dr Richard O’Brien, a pioneer in the field of zeta potential: http://www.chem.agilent.com/scripts/LiteratureResults.asp?iprodinfotype=4&imodel=1765

My recommendation - mix yourself a glass of chocolate milk - and read up on zeta potential.  Let me know how it goes! 

Nanoparticles in Drug Delivery

May 5, 2008 by Grant Drenkow

Although I’m not a medical doctor, I’m very intrigued with the possibility of nanoparticles becoming the drug delivery mechanism for the future.  Delivering small doses of medicines directly to cancer cells would eliminate the painful chemotherapy that many now have to suffer through.  I’ve had several friends who have gone through this misery and it’s something that I hope researchers and doctors can figure out.

The key is really to use the right sized particle, coated with a molecule that will attract itself to the diseased cell.  Once inside the cell the nanoparticle can deliver enough medicine to kill just that cell and not the healthy cells that may be around it. 

Agilent announced at Pittcon a particle size spectrophotometer that can measure the particle size distribution in the 5 nm to 15 um range - the sweet spot for these drug delivery nanoparticles.   Using our proven UV-VIS spectrophotometer technology the instrument is able to measure and display a wide distribution of particles in suspension in only 5 seconds.   Getting the right-sized nanoparticles should help researchers find the drug delivery mechanism of the future.

If you are looking for a good article on this subject check out this website — http://www.expresspharmaonline.com/20080415/healthcare01.shtml

If you want to learn more about the Agilent 7010 Particle Size Spectrophotometer, check out this website — www.agilent.com/chem/particles

Pittcon 2008

March 14, 2008 by Grant Drenkow

Last week I attended the Pittcon show in New Orleans.  It’s the largest chemical analysis show in the country with all the major analytical equipment suppliers in attendance.   New Orleans went all out to host this large event and it was good to see the city coming alive after Hurrican Katrina. 

From a nanotechnology perspective I was involved in the launch of Agilent’s new Materials Science Solution Unit (MSSU).   The purpose of this group is to focus on the transition of nanotechnology from pure research to new materials made up of nanoscale structures.   Our CEO, Bill Sullivan, hosted a press conference where he introduced Mike Gasparian, the VP / General Manager, of the MSSU.  Mike talked about the newest additions to the Agilent nanotechnology family of products - particle analyzers and optical fluorescence microscopes - and the acquisition of Colloidal Dynamics (known for their electroacoustic zeta potential measurements) and TLL Photonics (known for a revolutionary new digital microscope). 

I’ll have further blogs on these topics in the future - stay tuned.

If you want to know more you should click on TLL Photonics link or visit the Particle Analysis website at www.agilent.com/chem/particles

Rms roughness: the measurement that may sometimes be skewed.

February 4, 2008 by Joan Horwitz

To obtain a reasonable measure of surface roughness on the nanometer scale, people most often use the atomic force microscope (AFM) or the scanning tunneling microscope (STM), not only because they offer the required resolution, but also, and more importantly, because AFM and STM images are height-encoded. This means we can measure the dimensions of the features in these images both in the plane (in x and y) and out of the plane of the sample surface (in z).

In fact, roughness my be the single most frequently made measurement in industrial applications of the AFM, and certainly an important measurement in academic research applications as well.1

Typically, AFM users rely on root mean square (rms) roughness, Sq, as the measurement of choice. (A quick search on Google for “rms AND AFM” returned about 333,000 hits today.)2

\displaystyle S_q = \sqrt{\frac{1}{MN} \sum_{k=0}^{M-1} \sum_{l=0}^{N-1} [z(x_k,y_l)-\mu]^2}    (Eq. 1)

where μ is the mean value of the height, z, across all in-plane coordinates (x,y):

\displaystyle \mu = \frac{1}{MN} \sum_{k=0}^{M-1} \sum_{l=0}^{N-1} z(x_k,y_l)    (Eq. 2)

This measurement, rms roughness, has some inherent limitations that are often neglected. Reporting the rms roughness is almost always useful, but frequently inadequate in accurately describing surface topography in a meaningful quantitative way. In some cases, the consequence of not knowing (or ignoring) the limitations of rms roughness is misperceptions and making poor decisions.

The limitations of rms (roughness) are well-known to those who work often and in some depth with statistics and probability theory, but not to most AFM users. The upshot of these limitations can be summarize by saying that rms roughness measurement can give nearly or identically the same numerical result for two surfaces whose roughness are qualitatively different, or very different; sometimes so different that even a simple visual inspection of the AFM images will reveal.

One important reason rms roughness is sometimes inadequate is that it is computed indiscriminately towards the polarity of the height value at a given pixel, relative to the mean height value across all the pixels in the image. In other words, as the formula (Eq. 1) shows, height values smaller than and larger than the mean value end up contributing to the rms roughness the same way, i.e., as positive numbers. The result is that the rms roughness may measure (very) nearly the same for two different surface, one for example a flat surface with many holes, the other a flat surface with many peaks.

It is clear that to distinguish at least between these two kinds of surfaces, a different kind of parameter from rms roughness is required. Such a parameter exists, and in fact it exists in most if not all commercial AFM image processing software. It is called skewness, and it is not nearly as popular with AFM users as the rms roughness is. (A quick Google search for “skewness AND AFM” returned about 15,000 hits today). The skewness, Ssk, is defined in a way that can quantitatively describe the asymmetry of a height distribution about the mean (and from there, it gets its name):3

\displaystyle S_{sk} = \frac{1}{MNS_q^3} \sum_{k=0}^{M-1} \sum_{l=0}^{N-1} [z(x_k,y_l)-\mu]^3   (Eq. 3)

The formula is similar to the one for rms, but unlike rms (roughness), the skewness can take on positive and negative values as well as zero (even if the surface is not perfectly smooth), because each term in the double summation is raised to an odd power.
Depending on the way z values are recorded in an AFM image, the mean value, μ, itself can do the same (see Eq.2), that is, take on positive or negative values. The difference is that the appearance of the third power in the double summation in Eq. 3 means that those features whose height is farther above or farther below the mean μ; make relatively heavier contributions to the computed value of the skewness, as compared to features closer to the mean.

For a symmetric surface, that is, a surface the height of whose features are statistically evenly distributed around the mean, the skewness will render a value near or equal to zero–the height distribution is not skewed.

For our example, the skewness will measure positive for the flat surface with peaks, and negative for the flat surface with holes, and yet the rms roughness may measure the same or nearly the same for both. In this example, if the sample is a piece of metal bearing whose friction performance is to be improved, then, it may make a big difference whether the surface is flat with many holes, or flat with many peaks. To settle for the rms roughness then may be to ignore the skewness risk.

I wrote earlier that the limitations of rms roughness measurement are well-known to those who work often and in some depth with probability and statistics, but not to most AFM users. In case I planted any doubt that rms roughness is overly subscribed outside AFM image analysis too, here goes: Millions of people make pretty important decisions about money using statistics and probability often, but not all of them in much depth (that‘s why I italicized the “and“). The celebrated French mathematician Benoit Mandelbrot, the inventor of fractals, has studied the implications of ignoring the skewness risk by analyzing financial markets using models (including perhaps the most famous one, the Black-Scholes model) that assume market “roughness“ has a symmetric distribution (zero skewness). Mandelbrot’s alternative ideas about this subject were published recently.4

Some AFM images are more pleasing to the eye than others. The beauty of every AFM image though is that it is height encoded. The availability, in the form of numerical values, of all three dimensions of every feature in an AFM image, opens up a myriad options for statistical analysis of surface topography on the nanometer scale. These options exist neither in scanning electron and transmission electron microscopy (despite their superior resolution) because the images are slope-encoded, not height encoded. Nor do they exist in other techniques that do offer height encoding, but that lack the required resolution, for example, optical and stylus profiling.

AFM (software) manufacturers are aware of the implications of this advantage beyond what the average AFM user seems to know. They implement numerous formulas in their software (and provide print and electronic support documentation) to give the users options for statistically quantifying surface topography beyond rms roughness (including with fractal dimensions, for example). Surface skewness, or the coefficient of surface skewness, to be more exact, belongs to a family of mathematical functions that work with statistical distributions. There are others like it included in AFM image analysis software. It is up to the users to simply apply them and see what happens beyond rms roughness.

Fadrad Michael Serry
http://www.michaelserry.com/
serry@michaelserry.com


1STM is infrequently used in industrial applications, because it does not work with electrically non-conducting samples. This severely limits the kind of samples that are amenable to STM analysis.2The choice of symbols in the equations here is similar to those in the software package “Scanning Probe Image Processor“ from Image Metrology A/S, Lyngby, Denmark http://www.imagemet.com/.

3This is one definition of skewness; others exist. A list of some is available from Wolfram Research Corporation at http://mathworld.wolfram.com/skewness.html.

4Mandelbrot, Benoit B., and Hudson, Richard L., The (mis)behavior of markets: a fractal view of risk, ruin and reward, Profile Press, 2004, London, UK. ISBN 1861977654.

Nanotechnology and Football

January 24, 2008 by Grant Drenkow

A colleague and I were discussing some ideas for this nanotechnology blog when we jokingly commented that if we wrote it about the Super Bowl we would probably get a lot more people tuning in to read it.  Out of sheer curiousity I ran a quick Google check on football and nanotechnology and found this interesting article about a contest being run by the American Physical Society.  http://blogs.zdnet.com/emergingtech/?p=807

One can win the smallest trophy ever made and a $1000 in cash by creating a video that demonstrates some aspect of physics in American football.  The winner will be announced on Super Bowl Sunday.  Sounds like fun!  Time to dig out your camcorder and go to work. 

The trophy will be built at the Cornell NanoScale Facility (CNF) on a silicon wafer in the shape of a football field.  In case you win the world’s smallest trophy - Agilent would be very happy to sell you an atomic force microscope so you can see it!  (How’s that for a shameless plug!)

Separating the men from the boys

January 24, 2008 by Grant Drenkow

When one talks about nanotechnology it’s usually about building something small, maybe out of nanotubes or nanoparticles.  It’s about creating a structure that is stronger, lighter weight, more durable, more flexible, or in some way better when built from the ground up.  It’s rarely (if ever) about tearing something apart or breaking something down into smaller elements. 

 In the world of proteomics it’s about studying proteins, particularly their structures and the role they play in living organisms.  It’s about finding a specific protein of interest in a complex sample, or more specifically separating the protein of interest away from the abundant proteins in the sample.  Not exactly separating the men from the boys or the forest from the trees - but rather it’s the inverse.  It’s separating the baby from the giants or the needle away from the stack of logs.  Not an easy task when you’re dealing with nanoscale devices like proteins.   

 In this article a group at the University of Groningen, The Netherlands, used a liquid chromatograph-mass spectrometry (LC-MS) instrument with three columns to find the protein of interest.  They were able to separate the specific protein of interest away from the huge number of abundant proteins in the sample. 

Check out the application examples on the Agilent Nanotechnology website (www.agilent.com/find/nano) or click here to see this specific example of using an LC-MS for nanotechnology research.

Testing Mighty Mouse

December 17, 2007 by Grant Drenkow

With all the talk in the US about illegal steroid use in athletics, its good to hear about microarrays and bioanalyzers involved in more meaningful research.  The Kaneka Corporation in Japan is using a bioanalyzer to test the RNA of mice to see the effect of licorice flavanoids (not steroids) on gene expression.  I don’t think they will turn these mice into baseball players but it does show the versatility of a bioanalyzer.  The analysis of RNA will hopefully lead to cures to some of our most puzzling diseases.  It’s just another example of this nano world and the measurements that make breakthroughs possible.

Microwave Microscope

December 12, 2007 by Grant Drenkow

Just about the time you think you know every instrument that exists - someone comes up with a new idea.  University of Maryland researchers have come up with something they refer to as a dielectric microwave microscope.  The combination of a microwave source and a AFM probe allows one to send microwave signals to dielectric material and look at the signals that are reflected back to the probe. 

Is this really a microscope?  According to the dictionary - a microscope is an optical instrument having a magnifying lens or a combination of lenses for inspecting objects too small to be seen or too small to be seen distinctly and in detail by the unaided eye.  So in the true sense, this isn’t a microscope because there are no optics and lenses.  However, it does allow one to “view” phenomena that is too small for the naked eye.  And I use the term “view” pretty loosely - a chance to better understand and/or characterize an object (or in this case, dielectric material). 

From my perspective I think we’re going to see a lot more combinations of traditional instruments to characterize / view new types of materials.  I applaud researchers who have found ways to combine different sources and sensors in order to better explain the properties and structures of nano materials.  If you would like to share your combination instruments or solicit ideas on combinational instruments - write back to this blog or send me an email (grant_drenkow@agilent.com). 

We would love to start a dialog on this subject that might lead to better measurements which in turn leads to breakthrough research and hopefully to products to improve our world.  Pretty lofty thoughts - but what you can’t measure … you can’t improve. 

To visit examples of unique measurements in the nano world - check out these application examples.   http://nano.tm.agilent.com/index.cgi?CONTENT_ID=1361&User:LANGUAGE=en-US

 

Materials measurements

December 5, 2007 by Grant Drenkow

If you’re new to the nanotechnology world, you might want to read an article on materials measurements at the nanoscale.  I happen to know the author very well.  The article walks through all the various instruments for making measurements on nanotechnology materials.  Some of them will surprise you as a number of people are using electronic instruments to make surogate measurements.  Check it out - page 10.

http://www.home.agilent.com/upload/cmc_upload/All/amj3_09_11_07.pdf