Real nanobots !!!! (???)

With fancy chemicals being developed for new medicines, a question remains: how can we deliver the most bang for the buck? It would be ideal to have a microscale delivery truck, capable of delivering the drug to the precise location needed. This would also eliminate many side effects experienced through a general delivery of the drug.

 Catalytic nanoswimmers are being researched as potential cargo vehicles. They are tiny spheres, with one half coated with a reactive material. This side reacts with chemicals in the environment, and the energy of reaction is transmitted into motion forward. Attach a blob of drug to them, and they can move medicine. But questions remain about how to get them to go a specific direction, without having to babysit them. Can we make these trucks driverless?

One way to direct these particles is to establish a fuel concentration gradient. The particles will be ‘attracted’ to the hot spot, though they have no free will.

In a recent paper, researchers say while this approach is interesting, it can’t be the solution. After all, the fuel molecules are not necessarily always the signal you want the swimmers to react to.

They explore another signal: a pH gradient.

Hydrogel particles can swell or shrink in size when the acidity of the environment changes. Particles are  smaller in high acidity, and larger in low acidity. By exposing hydrogel catalytic swimmers to a pH gradient, the team was able to accumulate the swimmers in high pH regions. Cancer cells, as an example, can cause acidity changes.

So why does this accumulation happen? First, the high pH makes the particles larger, which makes their diffusion – the random motions experienced at the microscale – slower. Thus (smaller) particles in low pH regions will be kicked out more often, and settle in the high pH region. The smaller particles also undergo more (random) rotational motion, and this ends up being a double whammy for remaining happy in low pH regions.

I was struck by this paper as it was in nice contrast-and-compare to the run-and-tumble motion of E. Coli. bacteria, as is mentioned in the paper. Both systems are governed by the same physics, at the same scales. E. Coli turns its motor off to tumble and rotate, and figure out where the food is. It then turns the motor back on when it finds somewhere to go.  The catalytic swimmers have no such on/off switch, but can still get to where they need to go.


Adhesion, Geckos, and Technology

One of our earlier experiences with science comes in kindergarten. The teacher brings out the Elmer’s glue and we put macaroni on construction paper. The white viscous stuff acts to permanently bond the paper and pasta. As children we’re ignorant of the science beneath this and view glue as magic stuff. But if we could zoom in to resolve the detail, we’d see the long squiggly polymer molecules in the glue are grabbing onto the fibers in the paper as well as the starch fibers in the macaroni. The glue acts as an adhesive.

Adhesion refers to whether or not two different surfaces stick together. [Aside: cohesion refers to how molecules within a substance are attracted to one another, one might think of it as ‘self-stickiness.’] In our glue example, there are actually two interfaces of adhesion, the glue/paper and the glue/macaroni. There are different varieties of adhesion. There is chemical adhesion, which involves actually forming a new bond between the molecules of each surface. There is the physical, grabbing adhesion of glue mentioned before. There is adhesion due to electric charge. That static cling sticker dedicated to your alma mater on your car window uses this kind of adhesion. There is even yet another type of adhesion. Even if there is no chemical bond, polymer grabbing, or charge attracting two surfaces, there is still likely to be a force of adhesion called “van der Waals” adhesion. The precise details of van der Waals adhesion will not be explored here, but it is the same van der Waals interaction (sometimes referred to as ‘London dispersion force’) many learn about in high school chemistry. Van der Waals adhesion can be surprisingly strong, as we will see.

Geckos are quite amazing in their ability to perform seemingly impossible feats of climbing. They can even easily climb up and down a smooth glass aquarium cage, a surface with no obvious footholds! Yet if you hold a gecko in your hand their feet don’t feel especially sticky. Each of their toe pads is covered with about 100,000 setae, basically short hairs. The setae then split into hundreds of tips, each about 200 nanometers in diameter. These setae tips are what touch the glass, so there must be some type of adhesion between the tips and the surface to support the gecko’s weight. Autumn and coworkers [1] cleverly demonstrated the exact nature of this adhesion. Since they produce no glue, chemical and physical mechanisms were not on the table. However, there were two dry adhesion candidates: charged and van der Waals. The team let the geckos crawl up and down smooth surfaces that were charged differently. They performed equally well on both surfaces, pointing to van der Waals adhesion as the culprit.

However, since this adhesion is strong enough to keep the gecko firmly affixed to a wall, then how do they unstick? Geckos can crawl quite quickly, so there must be an unsticking mechanism in place. The same group came forth [2] to answer this question. With a series of experiments (including forcing a gecko to hang by one toe) the team showed that the setae tips are angled. This has the net effect of increasing the adhesion forces when at they are on surfaces at steeper angle: the setae tips become stickier as needed! Further, the angled attachment affords easy detachment: there is essentially no force required to move the foot up. They also have a “reverse gear” in their back feet for moving down surfaces, where the tips are oriented in the opposite direction.

Recently, Suh and coworkers [3] have been trying to recreate this remarkable gecko adhesion synthetically. After all, this adhesion has many desirable qualities. It’s strong, yet completely reversible. It can adhere to various degrees of surface roughness and any surface orientation. These qualities are especially suited to precise tasks such as moving and manipulating sensitive electronic components. The group was able to fabricate 200 nanometer plastic ‘hairs’ on a flat surface, resembling the setae tips of the gecko. These hairs were angled as well, and a 1 inch patch of them was capable of transporting a piece of glass that was 300 times that large! However, this system relies on needing to hit the hairs at the correct angle, and so is really a passive adhesion mechanism. While the gecko uses the same basic mechanism, it is actively controlling the contact with its muscles. Unfortunately, the synthetic version would not be suited to any complex task.

So while originally inspired by the gecko, the group ultimately developed a better system for practical use [4]. They stretched out a thick sheet of rubber and treated it with a reactive gas, so only the top surface was modified and became stiffer. When the sheet was allowed to relax, it went back to its original size. However, the top surface was no longer happy in this state, and created a wrinkly pattern on the surface, like a shallow egg crate. They then stretched it again, and put small (1/50th of a millimeter) pillars on the surface. So, when the sheet is relaxed, the pillars do not stick straight up, rather they are at odd angles due to the wrinkling, and when stretched they stick straight up. This creates a simple on/off adhesion mechanism. In the stretched state, the top of every pillar can make good contact with another surface, and in the relaxed state, none of the pillars can. They were able to pick up and move the same piece of glass in a complex choreography, all without leaving the even the slightest trace on the surface.

[1] Autumn, K. et al. PNAS 99, 12252 (2002)

[2] Autumn, K. et al. Journal of Experimental Biology 209, 3569 (2006)

[3] Suh, K.Y. et al. PNAS 106, 5639 (2009)

[4] Suh, K.Y. et al. Langmuir 26, 2223 (2010)

A reflection upon hard drives

A few months ago I was having an issue: my laptop’s hard drive was running out of storage space. I was in the heat of a project that I couldn’t put on hold so every day I had to find a few unimportant files to delete. Just five years ago this computer was state-of-the-art and had seemingly endless storage: 100 gigabytes of data. But, like a large purse, I found ways to fill it. The documents and photos didn’t take up so much space, but my music collection took up a large chunk. At the time I didn’t sweat it as the 40 GB or so of free space was surely enough for an eternity. But my music collection bloomed. To compound this, about a year ago I started a video collection and it was only a few weeks before it was filled to the brim.

After my project was done I knew I needed to reflect on the state of my laptop. The big picture was sunny: The outside still looked nice and not outdated, I upgraded the RAM a couple of years ago to give it some spring in its step, replaced the battery, and the processor was still capable. So instead of getting a new computer, I swapped out the hard drive for a new one. The new hard drive fit snugly in the old one’s spot. It boasted 500 GB of storage. I now had an amazing 400 GB of free space (which has sadly since declined to 300 GB).

ANSWER: How much more storage we get per square inch of hard drive material compared to 1956, the advent of the hard drive. QUESTION: What is one billion times more?

Today, you can put 40,000 mp3s onto a drive that fits inside of an iPod. In 1956, if you put just 1 mp3 file onto a hard drive, you would need a forklift to move it anywhere. A well-known rule of thumb in the computer industry is “Moore’s Law”, which predicts that the number of transistors on an integrated circuit will double every two years. Translation: your computer gets about twice as fast every two years. Similarly, hard drive storage has Kryder’s law: the storage per square inch doubles about every 2 years. My hard drive problem was a beautiful illustration of Kryder’s law in action. In the five years since I bought the original computer, the available storage (100 GB) in a hard drive that size should have doubled at least twice, which is what it did (500 GB). This type of growth is exponential, and this mathematical trend has held since 1956. The fact that the trend has held so long is pretty amazing, but peel back one layer and the story gets more interesting. It’s not a natural progression of one technology. Every few years we hit the wall with the current recording technology and someone has to develop something better. But someone always does come up with something and the trend marches on. One of these transitions happened around 2005 when “longitudinal recording” reached its limit and was replaced with “perpendicular” recording. Unfortunately, we’re now at the limit of perpendicular recording.

To understand the source of this limit let’s dig in to what a hard drive actually is. The main star of any hard drive is the platter: It is a disk containing magnetic material and this is where the information is stored. It is called a “drive” as the platter is forced (driven) to spin so that a stationary read/write head can read/write data at different locations on the platter. (Tangent: “Flash drive” is a misnomer as there are no moving parts inside your USB stick. The name persists as hard drives came before flash “drives” and both types can be interchanged in many systems.) It is called “hard” as the magnetic material has a high coercivity, which basically means that once it’s magnetized, it’s hard to demagnetize it. So once your data is written it will be permanently stored on the disk, unless of course you make a conscious choice to erase or overwrite it.

The magnetic material on the platter is not uniform. Rather, small islands of magnetic material coat the surface in a random mosaic, separated by thin channels of a nonmagnetic material such as glass. This is called “granular” recording media, as the islands of magnetism are called grains. Each grain corresponds to one bit of information: when you save a file, the recording head assigns each grain a 1 or 0 by forcing the magnetization up or down. The current grain size is about 10 nanometers. So to increase the storage for a given platter size (and continue the exponential trend) we will need to reduce the size of these grains.

However, it’s hard to make these islands smaller given the current uncontrolled deposition process. “Bit patterned media” has emerged to solve this problem. Using the same precision fabrication methods used to make computer chips, scientists can construct nanoislands of magnetic material that are uniform and evenly spaced, each island corresponding to one bit. It has been shown to increase the data density by several fold to 500 GB per square inch [1]. This process is not optimized yet, so the production of this media is expensive and the quality is not up to par.

But even if bit-patterned media becomes more efficient to produce, there is still another hurdle. Making the domains smaller increases the likelihood that they will spontaneously demagnetize due to random fluctuations. One obvious way around this problem is to increase the coercivity of the material. But this creates a new problem on the other end: it makes writing more difficult as a stronger magnetic field is needed to seal in the magnetization. A clever solution has been reached, called thermally assisted recording. Basically, a laser is shined onto the high-coercivity material to heat it up. This has the effect of temporarily reducing the coercivity, so writing is easy. Once the data is written, the laser is turned off and the information is sealed into the cooled-off material, restored to its normal high coercivity.

When combined together, bit patterned media and thermally assited recording have been shown to increase density up to 1000 GB (1 terabyte) per square inch [2]. If this combination can sustain the exponential growth, then in 2020 we should expect densities of 10,000 GB (10 TB) per square inch. When you dive into the details, this means each magnetic domain will be separated by only 1 or 2 nanometers. This corresponds to only 10-20 atoms. Thus 2020 might mark the limit of magnetic recording; we just can’t get any smaller!

So will magnetic media survive? Will it be taken over by some other new thing? Solid state (Flash) drives are gaining popularity for file storage. They are more physically resilient than hard drives since there are no moving parts to break. However, they are still much pricier than hard drives and concerns still loom about their permanence compared to magnetic storage. There are some other good candidates, for instance, phase change random access memory (PCRAM) and spin transfer torque random access memory (STTRAM) [3]. But no matter what ultimately wins, magnetic recording media will be around for a long time as it is cheap, well studied, and very permanent.

On the other hand, the question of survival may be moot to the future average consumer. Cloud-based storage is becoming more prevalent and might take over as our main file storage system. It’s similar to our current monetary system: while you carry some cash on you, most of your money is in a bank and can be accessed from any ATM. So in the future, your laptop’s hard drive (“wallet”) may actually have less storage than it does today and you won’t need to carry so much data (“cash”) on you. Most of your files will be stored on a central cloud that you can access from any computer. So while the companies that own the cloud (e.g. Google or Dropbox) will probably care about which recording medium they use for their massive storage banks, you might have your head in the clouds about the whole issue.

[1] Mate, Mathew. “How new disk drive technologies are pushing the nanoscale limits of materials and mechanics,” MEAM seminar, UPenn, 1 February 2011.
[2] Stipe, B.C. et. al. Nature Photonics 4, 484 (2010).
[3] Kryder, M.H and Kim, C.S. IEEE Transactions on Magnetics, 45, 3406 (2009).

How do you make a nanobot?

Here is an essay I wrote while reflecting on and researching a lecture I heard by Yale Goldman, Professor of Physiology at the Pennsylvania Muscle Institute, and associate director of the NBIC at Penn.

How do you make a nanobot?

Imagine you are playing with a set of Legos. This set is one of the newer

ones. It has all kinds of blocks, gears, wheels, pulleys, batteries, etc. Put different

combinations of them together and you can build a house or maybe if you’re feeling

clever, a machine. Suppose you make a small battery-powered car. Imagine shrinking

this car. As it shrinks, the number of atoms in each Lego block must become fewer.

Eventually, you may reach the limit where each block is one atom. What if we could

make machines like this?

Eric Drexler had this vision in his 1987 book Engines of Creation: The Com-

ing Era of Nanotechnology. He imagined if we could manipulate atoms like Legos,

we could build nanomachines from the ground up, atom by atom. One could create

different kinds of machines by simply using different assemblies of atoms. Drexler

hoped that these “nanobots” could be used to do all sorts of things, like deliver drugs

to specific sites within the body. Micheal Crichton in his 2002 novel Prey envisioned

these nanobots existing, but in a typical Crichton ending the bots take over and kill

us. While Drexler’s vision is intriguing (and Crichton’s vision is scary), these hopes

(fears) should be looked at skeptically. For starters, it’s simply not possible to build

nanomachines using Drexler’s scheme.

Why is this? Consider a Lego block floating in a cup of water. This block is

surrounded by water molecules. The water molecules are constantly jostling about

due to a phenomenon called Brownian motion. You won’t see the effect of this phe-

nomenon with the Lego. Change the Lego to a speck of dust. The dust is much

smaller than the Lego and so is more affected by the jostling of the water molecules.

(You can actually see the dust being randomly jiggled around if you do this experi-

ment.) Now, imagine changing the speck to a single sugar molecule, comparable in

size to the water molecules. What was gentle jiggling of the dust translates into vio-

lent jostling of the sugar molecule. In fact, the sugar molecule collides with the water

molecules about a trillion times per second! So we really can’t place atoms together

in an orderly fashion like we can with Legos: the wind is too strong. In brief, the

nanoscale is a much harsher environment than the macroscale.

Despite the seemingly impossible construction challenge of Brownian motion,

nanomachines are ubiquitous. They are around us and already inside of us! Fear not,

as they are supposed to be there. They are naturally occurring biological molecules

that keep us functioning. So in order to make artificial nanomachines, we might need

to steal ideas that nature is already using. Biological nanomachines make use of a

few tricks, that scientists one day hope to copy. First, their molecular makeup is pre-

programmed by a DNA sequence. Secondly, they undergo self-assembly to make up

their final shape. Lastly, they use the Brownian motion of the surrounding molecules

to their advantage rather than detriment.

One example of a natural nanomachine is myosin. There are several different

varieties of myosin. They are all motor proteins that “walk” along long actin fibers.

All myosins are actuators, machines that convert one form of energy to another. Like

the motor in a battery-powered car converts electrical energy into motion, myosin con-

verts the energy of a chemical reaction (ATP to ADP) into motion. Clearly myosin

is a great model nanomachine to study for future technology. One common variety

of myosin (II) is responsible for flexing our muscles by sliding the filaments against

each other. One variety (V), is responsible for moving large amounts of cargo along

actin fibers. Myosin V has two “hands”, and seems to move hand-over-hand along

actin, similar to a child on monkey bars [Corrie, J.E.T., et. al. Nature 422, 399

(2003)]. However there does seem to be a key difference. The child on monkey bars

releases one hand, then does a power stroke with the free hand to get to the next

rung. Myosin does the same motion, but its power stroke only takes it 2/3 of the

way. It then lets the Brownian motion of the surrounding water push the rest of the

way [Shiroguchi, K. et. al. Science 316, 1208 (2007)]. By taking advantage of this

Brownian motion the efficiency of the system is about 50%, very comparable to an

electric motor!

While artificial nanomachines are still only a vision, it’s clear that natural

nanomachines are excellent prototypes. Unfortunately, our technology is not at the

stage where we can really imitate them. What scientists can do (and are doing now)

is try to understand more deeply how these fascinating natural nanomachines work,

and use this understanding to inform future technologies.

[1] Drexler, Eric. Engines of Creation: The Coming Era of Nanotechnology, 1987

[2] Crichton, Micheal. Prey, 2002

[3] Goldman, Yale. “Nature’s Nanotechnology: Biomolecules Explored One at a Time” Penn Science Café Lecture, 20th October 2010.

[4] Corrie, J.E.T., et. al. Nature 422, 399 (2003).

[5] Shiroguchi, K. et. al. Science 316, 1208 (2007).

Cartoon of still SEM images of myosin processing along actin from: Matthew L. Walker, Stan A. Burgess, James R. Sellers, Fei Wang, John A. Hammer III, John Trinick & Peter J. Knight. Two-headed Binding of a Processive Myosin to F-actin. Nature, 405, 804-807 (2000).