A paper entitled 'Floating Tip Nanolithography' appeared in my RSS reader this morning. I make it a point to scoff when I see the nano- prefix being overused, but this got me questioning the whole field (assuming nanolithography is considered a field?), not just the world itself. There's too much nanostuff, but that's the point I'm making here. (And in the paper they do say: "NANO" revolution, sigh.) Why do nanolithography at all? Is this just some proof of concept idea?

The wiki entry tells me that it's used for creating microcircuitboards. Okay, that's useful enough, but from what I've seen from nanolithography papers, it's just people writing the names of their universities on a surface.



Here, a paper shows that by using a hot, floating AFM tip, they can get better resolution. They coat a gold surface with a polymer, then melt it off. Good, now you can write your name more clearly. With this method they were able to draw smaller images, with letters 100nm wide, while some of the older techniques (for example, physically scratching a surface with a sharp AFM tip) weren't able to clearly write.

Is there more to this field that I'm missing?

Milner, A.A., Zhang, K., Prior, Y. (2008). Floating Tip Nanolithography. Nano Letters DOI: 10.1021/nl801203c

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All I know about viruses I learned for the seminar that I gave a month ago or so. I've never taken biochem or virology, so there's my disclaimer.



Vaccinia (MVA) is a poxvirus, the class of viruses which includes smallpox. They're not fun organisms; the damage they do on cells is shown in the image above. MVA is a complex virus; it's not icosahedron or helical, and there's an intracellular and extracellular version. As far as viruses go, that's pretty complicated, they're generally more simple than this, structure-wise. Additionally, the Helenius group at ETH Zurich has been researching how they act as a trojan horse to cells.

MVA enters a cell by floating up next it, and blebbing it. Blebbing? It's essentially forming an amoeba-like arm and poking and prodding at it. Then, the cell tries to eat the virus, and bam, it's in. Wait, why? If I hear someone knocking at the door, I go look in the peephole. If I see a Jason mask and a shotgun, my first instinct is to not open the door. However, if they're wearing a Papa John's hat and holding a pizza, I'm going to open the door whether or not I ordered it. Do they have a Jason mask and shotgun behind their back? Who cares, pizza!



That's how MVA does its thing. Embedded on MVA's surface is phosphatidylserine (PS). This is present when other cells undergo aptosis, so it signals to the cell that there is going to be cell remnants left for it to eat. Then when it feels the poking and prodding of the blebbing, it starts to eat, and kaboom. That's why I chose an eating analogy. How do we know this is happening? They put different inhibitors onto the virus which will stop this from taking place. You can see from the graph below and the image above, this is effective in stopping the virus from entering. The black bars on the graph are the virus binding to the cell, and the white bars are the cells being infected. ANX5 is one of the inhibitors they tested.



I'd comment more, but uhh, I've told you everything I understand. I should take biochem one day.

Mercer, J., Helenius, A. (2008). Vaccinia Virus Uses Macropinocytosis and Apoptotic Mimicry to Enter Host Cells. Science, 320(5875), 531-535. DOI: 10.1126/science.1155164

Godspeed.

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In April's Journal of Solid State Chemistry, Honggang Fu's group published a paper on iron oxide nanoworms being used for water treatment. They don't actually use the term nanoworms; they just say "iron oxide with wormlike morphology", but nanoworms sounds cooler, and I've heard the term used before. Morphology is a good word, but it just doesn't match up.



Anyway, the idea is that they were able to create iron oxide that looks like it does in the image above. Creepy looking. They took iron nitrate, mixed it in with a big block copolymer and refluxed it. They have an idea of how it worked, the scheme is below, but this definitely seems like the kind of thing you just stumble upon when you're trying for something else. It's nice when science works out like that sometimes.



When they dipped it in solutions of chromium, it adsorbed onto the surface due to ion-exchange, and the nanoworms work better than a film of iron oxide because of the higher surface area. They got a higher removing capacity when they did the reflux at lower temperatures. This is seemingly because the nanoworms aggregate and anneal with higher temperatures, which would like to bigger worms (nanonightcrawlers?) and less surface area.

Worms: good for your compost, bad for your computer, but now good for your water purification.

WAN, L., SHI, K., TIAN, X., FU, H. (2008). Facile synthesis of iron oxide with wormlike morphology and their application in water treatment. Journal of Solid State Chemistry, 181(4), 735-740. DOI: 10.1016/j.jssc.2008.01.019

Godspeed.

[Comments: 0] [Tags: journals, science]

In an Inorganic Chemistry publication back in March 2008, Yadong Li's group at Tsingua Univ. synthesized CdSe nanoparticles that were small enough to fluoresce blue. Because of quantum confinement, nanoparticles (specifically quantum dots) fluoresce at shorter wavelengths with smaller radii. To synthesize quantum dots with radii this small is difficult; they must be smaller than 2 nm.



The method they employed was to first create nanoparticles by a microemulsion route, then mildly oxidize the nanoparticles to reduce them into smaller particles. The pretty picture you see above shows the nanoparticles after microemulsion on the left, then after further oxidation on the right.This was an effective route and they were able to create sufficiently small nanoparticles. I actually did a lengthy paper and presentation on the dynamics of nanoparticle synthesis by microemulsion this semester, so I enjoyed coming across a paper that employed it. It's advantageous because you can limit the nanoparticle size effectively.



The diagram above is the basic scheme for microemulsion synthesis. Basically, each microemulsion contains a reactant of the synthesis, and when they are forced together (in a reactor) exchange occurs and the reactants combine. Because there is limited reactant in each droplet, the size of the nanoparticle is controllable, and the size of the droplet regulates the size as well. The image is from this paper.

Anyhow, I enjoy the idea of using the sun in synthesis, but it kind of sucks for research labs that don't get too much of it. I don't see any problems with the paper - I'm pretty impressed. Maybe someday I'll make nanoparticles by a non-single source precursor method and will employ a microemulsion technique.

Liu, L., Peng, Q., Li, Y. (2008). An Effective Oxidation Route to Blue Emission CdSe Quantum Dots. Inorganic Chemistry, 47(8), 3182-3187. DOI: 10.1021/ic702203c

Godspeed.

[Comments: 0] [Tags: journals, science]

Back in March, I found a communication in JACS about determining the concentration of quantum dot nanoparticles by measuring their fluorescence burst counts by the Johnson group at York College. The QD solution (which could be in aqueous or organic solvent) was passed through a laser to induce the excitement and the different wavelengths emitted were separated by dichroic mirrors. The scheme is shown below.



They refer to this as a simple and accurate process. They do get good results, so I will give them accurate, but simple? I suppose if you work in lab that does a lot of laser chemistry, this might be simple, but not for me. Regardless, I don't think the method has that much going for it. There are other ways in which you can determine nanoparticle concentration, and other information about your system simultaneously. The one cool thing that this method does have going for it is that if you have a mixture of quantum dots that fluoresce at different wavelengths, you can measure both of their concentrations simultaneously.

However, back in 2004, there was a review in Accounts of Chemical Research, on using a carbon nanotube system to quantify nanoparticle concentration, by the Crooks group at Texas A&M. I wouldn't describe this as a simple system either, however. It involves embedding a carbon nanotube in an epoxy matrix, and creating an electrochemical system where the nanoparticles move by electrophoresis. A schematic is shown below.



The nanoparticles pass through the carbon nanotube, which has an ionic current passing through it. Based on the frequency and pulse height of the change due to the nanoparticle, they were able to obtain the concentration and nanoparticle size respectively. This has many advantages over the previous system. Firstly, the nanoparticles don't have to be quantum dots, non-fluorescing nanoparticles can be measured as well. Additionally, the nanoparticle size is being measured. This method is known as a Coulter counter.

These systems both have their pluses, but as you can tell, I prefer the carbon nanotube based system.

Zhang, C., Johnson, L. (2008). Simple and Accurate Quantification of Quantum Dots via Single-Particle Counting. Journal of the American Chemical Society, 130(12), 3750-3751. DOI: 10.1021/ja711493q

Ito, T., Henriquez, R.R., Crooks, R.M. (2004). A Carbon Nanotube-Based Coulter Nanoparticle Counter. Accounts of Chemical Research, 37(12), 937-945. DOI: 10.1021/ar040108+

Godspeed.


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Lindinger's group at the Nestle Research Center in Switzerland published a study back in March 2008 in Analytical Chemistry about analyzing coffee with mass spec. I read about this on Engadget then promptly forgot about it. I even gave a presentation on it for my Analytical class, only later to see this in my RSS bookmarks.

Basically by using PTR-MS (proton transfer reaction mass spectrometry) they did an analysis of different coffees. They emphasized that this was a data-driven study, not a chemical analysis study, because they weren't necessarily analyzing the different compounds individually. Rather, what they were doing was taking the results of the mass spec, then combining them with the 'results' of a 10-member panel of coffee experts to create a model. So they just took the intensities of the different peaks (all the compounds that had 108 m/z, 110 m/z, etc.) and compared them to the 'intensities' of the panel ratings. A rough scheme is shown below.



The panelists rated the intensity of different qualities (coffee, bitter, cocoa, roasted, woody, cereal, butter toffee, acid, citrus, winey, and flowery) of the coffee. They ran a blind study, and the panel was able to produce reproducible results, so they apparently know what they're doing. I would imagine they look something like this:



Once the model was created, they did PTR-MS on another set of coffees, had the panel do their tests, then compare how well the model was able to predict it. You can see in the graph below that they were pretty successful. You can see that there are only 8 qualities below; they decided to scrap a few qualities, but didn't really explain why. The ones that they got rid of were: winey, flowery, cereal. You can assume that they took those out because they didn't fit with the model as well, and that's probably because those qualities are made up. Nobody drinks coffee and thinks, oh that was nice and flowery. But not winey enough. Nonsense.



I'd like to see them create a model that determines if coffee is good or bad. Sure, that's even more arbitrary, but it's more useful. Then we could take samples from a bunch of different coffee shops, and finally scientifically prove that Starbucks' coffee blows.



Lindinger, C., Labbe, D., Pollien, P., Rytz, A., Juillerat, M., Yeretzian, C., Blank, I. (2008). When Machine Tastes Coffee: Instrumental Approach To Predict the Sensory Profile of Espresso Coffee. Analytical Chemistry, 80(5), 1574-1581. DOI: 10.1021/ac702196z

Photo: Louisiana State Museum
Photo: Flickr

Godspeed.

[Comments: 2] [Tags: food, journals, science]

A paper was published in JACS (see below for reference) a couple months ago by the Matsui group at CUNY Hunter. The idea is that you can uniquely identify a virus by measuring its electrical properties.



We're not talking about a solution of viruses, this is measuring the electrochemistry of one individual virus particle, a virion. I'm not going to go into the details of the method, otherwise this post would be pages long, but the gist is that you put a virus onto a film of gold, locate the virus with AFM, then use the AFM tip and the gold film as electrodes and run AC current through it. You can get a unique signature by looking at the capacitance versus frequency. The results for five viruses: AV5, SV40, MVA, CPMV, and HSV1 are shown below.



You can see that each virus is distinguishable from one another by both the pattern of the line, as well as the magnitude of the capacitance; there's overlap in a couple of places, but you can still distinguish them from each other. The paper stated that the unique identification of these viruses is made possible through the difference in protein compositions, which have different dielectric constants.

They left out quite a few important aspects in this paper. I talked to a virologist to learn more about viruses, which showed me many things they omitted. It makes sense since their flaws lie mostly on the biology side, because they really only spent a couple sentences talking about viruses themselves.

Firstly, they make little to no mention of the viruses size. They state that they range from 30-300 nm and give their sizes, but don't discuss any possible contribution. If you look at the equation for a parallel plate capacitor, you see that the distance between the electrodes plays a role. We can't use that equation here, but the concept still remains.



Secondly, even less mention of the viruses shape is included. Four of the five viruses they studied are icosahedrally shaped, so they can be treated roughly as spheres, but one is more complex than that. That complex virus is MVA, and an image of it is shown above. Additionally, they don't mention that there is an entire helical class of viruses which could be studied. Based on their orientation on the film, would they give different results, since there would be a different distance between the electrodes? Would this cancel out since they're measuring more than one virus and averaging?

Lastly, not all viruses are stable outside of a host cell, so this can't measure all viruses, which is a pretty big limitation. There's a chance that they could measure an infected cell rather than a virus particle in order to identify the virus, but that seems unlikely given the large 'background noise' the cell would provide, and it would be hard to factor in all of the different stages of infection.

Overall, the paper is good - it's a pretty novel idea, but it definitely needs more work. I could go on a lot more about this, since I gave my 25 minute long Graduate Student Literature Seminar on this paper, but I won't.

MacCuspie, R., Nuraje, N., Lee, S., Runge, A., Matsui, H. (2008). Comparison of Electrical Properties of Viruses Studied by AC Capacitance Scanning Probe Microscopy. Journal of the American Chemical Society, 130(3), 887-891. DOI: 10.1021/ja075244z

Godspeed.

[Comments: 0] [Tags: journals, science]

I'm definitely not sold on global warming one way or the other. I don't think there's enough data to rule it out or prove it, but I do think research should continue. I'm not so sure I would sue Al Gore over it, though the idea is entertaining. I bring this up because I came across a 2006 paper from the Annual Review of Physical Chemistry, "Atmospheric Field Measurements of the Hydroxyl Radical Using Laser-Induced Fluorescence Spectroscopy". I found this in search of a paper to write about for my dynamics class, and I think I'll use it.



For the most part, I enjoyed the paper, which is surprising given the amount of analytical and physical chemistry within. To say the least, they are far from my favorite subjects (even though I'm taking both this semester...). It also led me to discover the MCM; the Master Chemical Mechanism, which I spent some time browsing and was pretty impressed with.

I have a few criticisms here, the first of which being they're trying to write a novel. Here's what I mean:
p. 193: "The most important of these intermediates is the hydroxyl radical (OH), which is generated mostly in the daytime as a result of ozone photolysis to form electronically excited oxygen atoms, O(¹D), which react rapidly with water vapor to form OH."
p. 210: "The main contributor to OH initiation in both summer and winter is the reaction between O₃ and alkenes." ... "The fraction of OH initiation from O₃ + alkenes is approximately double that from the O(¹D) + H₂O reaction in the summer, but 100 times greater in the winter.
p. 212: "The largest source of OH by far is the reaction of HO₂ + NO, and thus OH levels reflect the rate of carbonyl photolysis, which occurs at longer wavelengths and thus is still significant in winter."

They're trying to guide us through the path in which they discovered things (I think), but it doesn't seem appropriate in the way they are writing things. My other criticism is that they talk about global warming without mentioning it's a theory. I know some people think that it has progressed beyond being a theory, but they should really be more objective in the scientific literature.

Edit:
Following up Martin's comment, I feel like I should clarify some things. I went through and reread what I have written on this issue, and gave it some thought. Criticizing the article for not referring to global warming is a theory seems rather silly now that I think about it, even though evolution (since it's the example that was used) is a theory, it's not really necessary to refer to as such. As for my personal views on global warming - I stand by that I'm not sold 100% one way or the other, however it's not the fact of whether it's happening that I question, rather the degree to which it's happening. I'm just arguing that people often exaggerate how fast this is taking place.

Heard, D.E. (2006). ATMOSPHERIC FIELD MEASUREMENTS OF THE HYDROXYL RADICAL USING LASER-INDUCED FLUORESCENCE SPECTROSCOPY. Annual Review of Physical Chemistry, 57(1), 191-216. DOI: 10.1146/annurev.physchem.57.032905.104516
Btw, I dislike DOIs that are this long.

Photo: Flickr

Godspeed.

[Comments: 4] [Tags: journals, science]

In my continued search for a paper to do my graduate student literature seminar, I came across this interesting paper.

Published about three weeks ago the web in JACS, researchers at the National University of Singapore have found a way to easily detect mercury in water. The method they are developing is very efficient because it can be performed in the field, without instrumentation, using just the naked eye in about 5 minutes.



Gold nanoparticles (NPs) are functionalized with two different strands of DNA - half of the NPs are functionalized with one strand, the other half with the other. Another strip of DNA twice as long is also added in the mixture. It is designed in a way that this long strip of DNA would not match up with itself, nor will any section of it match up with the two shorter strips that are bound to NPs under normal conditions. However, the system is designed so that the longer strip will bind with the two shorter strips (essentially taping two NPs together) if thymine (the T in GCAT base pair matching) would bind with itself. Mercury has a feature which is rather unique to it, in that it coordinates thymine bases in DNA to one another so that there is a mercury-thymine-mercury connection. Since this is unique to mercury, this method will ignore other metals such as lead, copper, calcium, and many others. The result of this is that nanoparticles will exist as free floating single units in a media which is free of mercury, however, with mercury present the nanoparticles will begin to connect to one another, and form a network, referred to as an aggregate.

Aggregation will show up as a color change. The science behind the color change is that the nanoparticles show a strong UV-Vis (ultraviolet-visible) absorption at a certain wavelength, which varies based on the size of the nanoparticle. This wavelength will change when an aggregate forms, and since color is based on the wavelength of light, this can be observed since these wavelengths are in the range visible to the human eye. Additionally if this aggregate grows large enough (and forms a polymer), precipitation can be observed in the solution.

Unfortunately, the amount of mercury present must be on the micromolar scale, which is a thousand more times more concentrated than the nanomolar scale, which is where the border between the acceptable and unacceptable levels of mercury lies according to the EPA. The current solution to this is to simply boil water down on site, however this does add to the work and time required for detection. This was published in JACS as a communication, and in their conclusion they talk about their plans for future work which would allow detection on a smaller scale by improving upon this method.

Xue, X., Wang, F., Liu, X. (2008). One-Step, Room Temperature, Colorimetric Detection of Mercury (Hg2+) Using DNA/Nanoparticle Conjugates. Journal of the American Chemical Society, 130(11), 3244-3245. DOI: 10.1021/ja076716c

[Comments: 0] [Tags: journals, science]

I'm a bit late posting on this, since it was published on the web in JACS almost a month ago... but oh well. Jones talks about the two conventional approaches to CO₂ capture - absorption into amine solutions and adsorption into porous silica systems. Their approach is take these methods and efficiently combine them into a method which uses both of their strong points.



As you can see in the diagram above, (and if not, I'm explaining it) the amines are bound to the surface of the silica. The result is referred to as a "hyperbranched aminosilica material". This is abbreviated as SBA-HA, for a reason which is not that clear. I had to look into this for a while before I could figure it out, but the SBA stands for 'Santa Barbara Amorphous type material', since the mesoporous silica was discovered at UC Santa Barbara. They show SBA-HA to bind CO₂ more efficiently than previous materials, and best of all - reversibly.

Reversibly binding CO₂ is an effective means of CO₂ capture because the material can be flushed out (in this case with argon), and be used again. This would be applicable for use with flue gas, which essentially just means gas that comes out of a smokestack. Jones reported up to 12 cycles without a loss in capacity though for industrial uses this would need to be tested on a much longer timescale. The next logical question in terms of application would be to figure out what to do with the CO₂ once captured.

In searching for related materials, other than finding out I was far from the first person to write about this, I also discovered that a patent was filed for the writers of this paper. Among other things, this paper corrected my previously ignorant idea that absorb and adsorb were just different spellings of the same word... the former means pulling a substance into solution, whereas the latter means pulling a substance onto the surface of a material.

Very interesting stuff; I'll keep this topic in mind when choosing a paper to discuss for my "Graduate Student Literature Seminar".

DOI: 10.1021/ja077795v

Godspeed.

[Comments: 0] [Tags: science, journals]

I decided that I should probably start regularly reading science journals. Since I also should be updating Will and Beyond with content, why not combine the two? Every week I will read through 'Science' and will summarize any articles I find interesting. If I didn't find anything that caught my interest, or I feel like doing more, I will look in other journals as well.

This week I looked at Science, Vol. 317, No. 5844, 9/14/07. Nothing really caught my interest, so I looked in the Journal of the American Chemical Society, JACS, Vol. 129, No. 37, 9/19/07.

Here, two articles caught my eye.

Modular Total Chemical Synthesis of a Human Immunodeficiency Virus Type 1 Protease

Human Immunodeficiency Virus Type 1 is more commonly known as HIV-1, the more widespread and contagious form of HIV. HIV-1 protease (HIV-1 PR) is a component of HIV-1 which is present in propagation/reproduction of the virus within the body. The exact catalytic mechanism of this is currently unknown. Being able to synthesize this protease would help us further understand it, and come closer to knowing exactly how the virus reproduces itself.

HIV-1 PR is composed of 2 99-residue polypeptide chains. This means that each of the 2 chains has 99 amino acids bound together in a certain sequence. In order to fully synthesize the protease, 4 smaller chains, about 25 peptides long were made by SPPS, solid phase peptide synthesis. The 4 chains were to be bound together with native chemical ligation, where they are connected by amide-thiol bonds. The thiols are later removed by Ramel nickel desulfurization.

However, when this was attempted, precipitation issues were encountered; the products would aggregate (clump up) and come out of the solution as a solid. In order to prevent this, another tactic was attempted; strings of the amino acid Arginine were bound to the end of one of the 4 small peptide chains. Arginine has been found to keep polypeptides in solution, though the reason is still unknown at this point. 10 Arginine units were bound to one of the 4 chains, and then each of the other chains was able to be connected one by one. The new issue arose of how to remove the Arginine once the 99 peptide chain was constructed. They thought that once constructed, the protease would act as it does when in the body and attempt to begin reproduction. The first step of this is to cleave the end of the chain and bind to another unit. This was successful.

The final product was made in 12% yield, which is a relatively high yield compared to other methods of creating peptide chains. The reaction took about 4 days, and was characterized (identified/verified) by LCMS (Liquid Chromatography Mass Spectroscopy) and MALDI (Matrix Assisted Laser Desorption/Ionization). These methods both take the mass of the product, which can be compared against the theoretical mass. An x-ray structure of the product was obtained by X-ray Crystallography and the product was seen to be bonded together as hoped.

This is a good step in the process, and the novel way that this was made keeps it free from contamination from enzymes which are encountered with other synthetic methods.

DOI: 10.1021/ja072870n

Paclitaxel-Functionalized Gold Nanoparticles



Paclitaxel is a drug which is used in cancer chemotherapy. Traditional drug delivery methods are not effective for all drugs; one major issue is that the hydrophobic nature of some drugs prevent it from being dissolved in the bloodstream and administered normally. A method to circumvent this problem is to enclose the drug in a hydrophobic surrounding, known as a micelle. However, a problem with this method is that this results in a very large product and this can be caught in the reticuloendothelial system, the RES, which is a system to fight foreign substances in the body, and is composed of part of the bone marrow, thymus, and liver.

Another approach is to make a smaller delivery system to avoid capture in the RES. This is done through nanoparticle delivery. Molecules of the drug are embedded onto the surface of a small metal nanoparticle. Gold is a common choice because of the ability to put organic groups onto it through an alkane-thiol bond. Even with this method, there are still problems - it can only be measured qualitatively because it is hard to characterize because of issues with solubility. They found that by using a 2 nm gold core, these issues don't arise.

Paclitaxel was bound to a hexaethylglycol (HEG) chain. A phenol thiol (4-mercapo-phenol) was bound the surface of the gold particle and these two were linked together by combining the carboxyl terminated end of the HEG with the phenol to form an ester. The HEG was chosen as a linker because it increases the solubility in water, and also minimizes destruction of the drug by the RES (which is called opsonization).

This was performed successfully. It is a 9 step process, of which many steps show 90%+ yield. The final product was characterized by NMR and (nuclear magnetic resonance) IR (infrared) spectroscopy. SEC (size exclusion chromatography) showed a good yield of the product with no side reactions resulting in small products. It was shown through TGA (thermogravimetric analysis) that there are approximately 73 (+/- 4) molecules per particle, which results in about the nanoparticle being composed of 60% Pacitaxel, which is an extraordinarily high organic to metal ratio. The product was also seen through TEM (transmission electron microscopy). This novel approach will be able to be used for lots of applications in drug delivery.

DOI: 10.1021/ja075181k

Godspeed.

[Comments: 1] [Tags: science, journals]