Have you ever done a ‘leadership’ exercise? I’m sure you know the sort of thing – You’re on a corporate “training day” and after being placed into arbitrary groups in a stuffy meeting room, you are given a handful of straws, paperclips and plastic cups and told to build a tower that reaches the ceiling. … Continue reading »... Read more »
Spisak, B., Homan, A., Grabo, A., & Van Vugt, M. (2011) Facing the situation: Testing a biosocial contingency model of leadership in intergroup relations using masculine and feminine faces. The Leadership Quarterly. DOI: 10.1016/j.leaqua.2011.08.006
Buffer This animation film was submitted by a med student to YouTube for the instructor of a course about ‘Narratives of Ageing:Exploring Creative Approaches to Dementia Care’. Students visited a locked unit at a care facility for people with Alzheimer’s disease. They used YouTube to watch streamed video made by Alzheimer’s disease advocacy groups, twitter [...]
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George, D., & Dellasega, C. (2011) Social media in medical education: two innovative pilot studies. Medical Education. DOI: 10.1111/j.1365-2923.2011.04124.x
A research group at the University of Indiana has developed a program called Truthy that allows anyone to track cases of “astrotweeting”. Any search term can be entered into Truthy and the program will scan the Twitter API and build a model of how the search term originated. ... Read more »
Ratkiewicz,J. Conover,M. Meiss,M. Gonçalves,B. Patil,S. Flammini,A. Menczer, F. (2011) Truthy: Mapping the Spread of Astroturf in Microblog Streams. World Wide Web Conference Committee (IW3C2). . info:/
fMRI used to create a video output based on a dictionary created by showing participants 7200s of random colour video.... Read more »
Nishimoto S, Vu AT, Naselaris T, Benjamini Y, Yu B, & Gallant JL. (2011) Reconstructing Visual Experiences from Brain Activity Evoked by Natural Movies. Current biology : CB. PMID: 21945275
You could say that valves in microfluidics (or microvalves) are like street lights that control traffic along microfluidic channels. But I’d say that they’re more like police barricades, stopping anyone they want, wherever they want. The sole purpose of microvalves is to control flow within a microfluidics device, allowing them to become very complex and more automated. Without microvalves, all reactions and mixing must occur in the same space, unless they were premixed elsewhere, which might just eliminate the advantage of microfluidics.... Read more »
Elizabeth Hulme, S., Shevkoplyas, S., & Whitesides, G. (2009) Incorporation of prefabricated screw, pneumatic, and solenoid valves into microfluidic devices. Lab on a Chip, 9(1), 79. DOI: 10.1039/b809673b
Hey, how’s your biotin? What? No it’s not an organic metal, maybe you call it B7? You’re probably fine, but have you been depressed, lethargic or losing your hair lately? Biotin is pretty important; it’s necessary for metabolism within our cells, so I make sure I never leave home without it. It’s rare for someone to have a biotin deficiency, but if you want to know your levels, give me a drop of your blood, and I’ll have an answer from you in 10 minutes. How? Oh just my self-powered integrated microfluidic blood analysis system (but I like to call it SIMBAS for short)...... Read more »
Dimov, I., Basabe-Desmonts, L., Garcia-Cordero, J., Ross, B., Ricco, A., & Lee, L. (2011) Stand-alone self-powered integrated microfluidic blood analysis system (SIMBAS). Lab on a Chip, 11(5), 845. DOI: 10.1039/C0LC00403K
Buffer Some research has been done on factors influencing a persons likelihood to play online games. All these motivations found in research doesn’t say much about the sources of these motivations. This study looks at how personality traits motivate online game play. This study was done in Korea. In Korea, watching television, going to the [...]
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Park, J., Song, Y., & Teng, C. (2011) Exploring the Links Between Personality Traits and Motivations to Play Online Games. Cyberpsychology, Behavior, and Social Networking, 2147483647. DOI: 10.1089/cyber.2010.0502
Microfluidic chemostat used to study microbes
I don’t quite have the resources to poll the United States and the rest of the world, but if I did, this is what I’d ask:
Do you know what microfluidics is?
Can you explain it to me?
Do you currently use anything with this technology?
We may never know the results of the poll, but I think I'd hear "No" for most of them. Have no fear, because today you’re lucky enough to read my Beginner’s Guide to Microfluidics.
To start with...... Read more »
Device which lets sound travel one way, but not in the opposite direction... Read more »
Boechler, N., Theocharis, G., & Daraio, C. (2011) Bifurcation-based acoustic switching and rectification. Nature Materials, 10(9), 665-668. DOI: 10.1038/nmat3072
Cardiopulmonary BypassCardiopulmonary Bypass (source) More than 1,000 adult and 50 pediatric patients undergo a surgery involving cardiopulmonary bypass (CPB) each day in the United States. A CPB is used when performing surgery on the heart or lungs, leaving them unable to perform their normal functions. But CPB introduces a lot of foreign material to the body, creating adverse reactions. The CPB assembly, drugs and surgical processes can each have their own inflammatory effects. Induced inflammatory responses may include the release of pro-inflammatory cytokines, endothelial dysfunction and complement, neutrophil and platelet activation. Analyzing the patient’s blood during CPB is necessary to tie an inflammatory response to its origin in order to reduce a systemic inflammatory response syndrome (SIRS). But in order to monitor the patient’s status, at least three ml of blood must be drawn from the CPB system each time. This blood must then be centrifuged to access its plasma component (read more about replacing the centrifuge). Three ml of blood isn't needed to get an accurate reading, but it fits into the current operating procedures. This looks like the perfect opportunity to implement a microfluidic device to continuously filter small volumes of plasma from the CPB system to be analyzed, which is exactly what researchers from Rutgers University did.MicrofilterFilter membrane sandwiched between channels The article“Microfiltration platform for continuous blood plasma protein extraction from whole blood during cardiac surgery” by Jeffrey Zahn et al. is featured in the 2011 issue 17 of Lab on a Chip. The authors wanted to create a lab-on-a-chip component to filter plasma from CPB while collecting only 50-100 µl every 15 minutes, which could be used for the duration of a procedure which may last four hours. The proposed device is simple and features two microfluidic channels separated by a semipermeable membrane. In order to increase the filtration rate, the device features 32 channels in parallel. The authors chose to use a membrane with a 200 nm pore size, which allows plasma and proteins of interest to cross into the filter channel while stopping the 6-8 µm red blood cells (RBC). Even though the pores are sized so that only proteins and plasma can pass, that doesn’t mean that they’ll always be able to do so. Some proteins and cells naturally adhere to foreign objects, creating a clot. We don’t want this to happen to our membrane, which could become mostly or completely clogged. While our pore size allows proteins and plasma to pass through at a faster rate than smaller pores, it is more likely to ensnare a cell that can’t pass through. In order to prevent the membrane from clogging, we can introduce an anticoagulant, such as heparin. Anticoagulants like heparin prevent blood from clotting by disrupting a series of reactions that occur in blood (To learn more, check out this video on Coagulation Cascade from Johns Hopkins University). We normally don’t want anticoagulants in our blood because it would stop us from healing, but they are used in surgeries to diminish reactions to tools or processes. Instruments can be coated with heparin, which the authors did for the filtration device, so that heparin doesn’t have to be added system-wide. The blood’s hematocrit (Hct) also affects the need for an anticoagulant. Hct represents the percent of the blood volume that is occupied by RBC. The mathematical maximum value would be 1, which would mean that the blood was entirely composed of cells and there was no plasma, while 0 would indicate that there are no cells in the blood. Therefore a higher Hct would have a higher density of cells passing through the device and would need more anticoagulant. The final device by the authors was able to deliver cell-free plasma which made up 15% of the blood volume. The authors noted that although the plasma is cell-free, they needed to verify the extent of hemolysis. Hemolysis is simply the destruction of (RBC). We don’t want this happening to our filtered blood and need to make sure this isn’t the reason that no cells are entering our filtrate. I think that this is a simple, yet needed piece of equipment. It is basically a membrane separating two microfluidic streams. Although the channels are small, (the largest width is no greater than 600 µm) the channels across the membrane are different sizes so that they will still align when put together by our imperfect hands. The construction of parts of the device must be precise, but the device becomes more accessible if it does not need a robot to assemble it. This still needs another attachable point-of-care device to actually test the plasma, but this is promising.Reference:Aran, K., Fok, A., Sasso, L., Kamdar, N., Guan, Y., Sun, Q., Ündar, A., & Zahn, J. (2011). Microfiltration platform for continuous blood plasma protein extraction from whole blood during cardiac surgery Lab on a Chip, 11 (17) DOI: 10.1039/C1LC20080A... Read more »
Aran, K., Fok, A., Sasso, L., Kamdar, N., Guan, Y., Sun, Q., Ündar, A., & Zahn, J. (2011) Microfiltration platform for continuous blood plasma protein extraction from whole blood during cardiac surgery. Lab on a Chip, 11(17), 2858. DOI: 10.1039/C1LC20080A
Buffer Because Facebook use can evoke a positive emotional state. Researchers have esthablished these positive responses during an expirement in which they measured several psychophysiological measures. They recorded skin conductance, blood volume pulse, electroencephalogram, electromyography, respiratory activity, and pupil dilationstate. They measured these psychophysiological patterns in 30 healthy subjects during relaxation condition, showing slides of [...]
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Mauri, M., Cipresso, P., Balgera, A., Villamira, M., & Riva, G. (2011) Why Is Facebook So Successful? Psychophysiological Measures Describe a Core Flow State While Using Facebook. Cyberpsychology, Behavior, and Social Networking, 2147483647. DOI: 10.1089/cyber.2010.0377
CartilageOur bodies are pretty much amazing. We can get hurt, and our bodies will heal our cuts and bones (with the right support). But not everything heals so easily, like cartilage. The cartilage in our joints is called hyaline cartilage and can be damaged from trauma or diseases like osteoarthritis. The other cartilages like elastic cartilage (found in our ears and nose) and fibrocartilage (found on tendons and ligaments) are a bit of a different story. The hyaline cartilage found on the articular surfaces of our bones can't heal like other parts of our body because it doesn't contain any blood vessels. The blood vessels would normally provide the cells and proteins to the damaged tissue. So, without blood, the damaged tissue pretty much does, nothing. Enter tissue engineering.Cartilage EngineeringWhen faced with something that won't fix itself, our initial impulse is to replace it. That was our first reaction too, but we can't replace cartilage with just anything. It is a very complex and dynamic tissue. Ideally we would replace it with fresh cartilage, but it's not so easy to grow. The engineered cartilage must have a functional shape, achieve specific mechanical properties and not cause an immunogenic response when implanted in the body. In order to encourage cartilage cells (called chondrocytes) to form tissue in three dimensions instead of the two-dimensional bottom of a dish, tissue engineers have been developing scaffolds. Scaffolds have four desired traits:Highly porous with interconnected network for cell growth and transport of nutrients and metabolic waste
Biocompatible and bioresorbable so that it can be replaced by the tissue
Ideal surface for cell attachment and proliferation
Mimic cartilage mechanical properties
Choosing the right material is pretty important, but devising a way to create a porous 3D network is also vital. Cells can't be cut off from transport of nutrients and waste, even though it's crazy to believe that chondrocytes only make up 1% of the volume in cartilage. Researchers at National Taiwan University have developed a new method to build cartilage scaffolds using a polymer called alginate, which is a gum extracted from seaweed. It has been used previously in other scaffolds, but the main advance made by the researchers is how it is manipulated. Microfluidic-generated Scaffold
The work by Feng-Huei Lin et al. is entitled "A highly organized three-dimensional alginate scaffold for cartilage tissue engineering prepared by microfluidic technology" and appears in the October issue of Biomaterials. The authors have developed a novel microfluidic method for creating the alginate-based scaffold. As depicted in their figure, alginate droplets are formed around nitrogen gas. Their formation is highly controlled resulting in monodisperse droplets, which means that they're all (statistically) the same in size and shape. These droplets fall from the device into a solution containing calcium ions. The calcium ions (Ca2+) cause the alginate to form a gel. But before that happens, the droplets form a pretty honeycomb pattern. While this looks nice, it has a very important function. Remember when I said that scaffolds need to have interconnected networks? Well the monodisperse droplets are able to align so that they fit together perfectly, creating hexagonal patterns around each droplet. Once the droplets have gelated, a vacuum is applied which removes the air bubbles and connects the network.This technique has seen some promising results when looking at how the cells attach, proliferate and survive. But some forms of alginate have been known to cause immunogenic responses which would be unattractive. Any resulting engineered tissue would need to be mechanically tested, which was not performed in this study.Overall, this research was pretty interesting. It's obviously relevant to us humans, but it also excites me because it is a form of therapeutic microfluidics. As you can see from the rest of my posts, a lot of microfluidic technology is used in diagnostics. Both are equally important, but occur in different frequencies, so you can understand why this would have a place in my heart.References:
Hutmacher, D. (2000). Scaffolds in tissue engineering bone and cartilage Biomaterials, 21 (24), 2529-2543 DOI: 10.1016/S0142-9612(00)00121-6... Read more »
Hutmacher, D. (2000) Scaffolds in tissue engineering bone and cartilage. Biomaterials, 21(24), 2529-2543. DOI: 10.1016/S0142-9612(00)00121-6
Temenoff, J., & Mikos, A. (2000) Review: tissue engineering for regeneration of articular cartilage. Biomaterials, 21(5), 431-440. DOI: 10.1016/S0142-9612(99)00213-6
Wang, C., Yang, K., Lin, K., Liu, H., & Lin, F. (2011) A highly organized three-dimensional alginate scaffold for cartilage tissue engineering prepared by microfluidic technology. Biomaterials, 32(29), 7118-7126. DOI: 10.1016/j.biomaterials.2011.06.018
Buffer Surgeons not being the most social animals among doctors, I was surprised to see 7 editorials about surgery and social media. These seven editorials highlighted the use of social media and different settings for surgeons, from medical school all the way up to the American College of Surgeons. The most factual contribution was about [...]
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Weinstein, A., Saadeh, P., & Warren, S. (2011) Social networking services: Implications for the next generation of physicians. Surgery, 150(1), 15-16. DOI: 10.1016/j.surg.2011.05.026
The extent to which someone develops their passion and calling for is affected by when they are exposed to it, if it all. It wasn't until 2009 (the summer before my junior year) that I was first exposed to microfluidics when Dr. John T McDevitt came to Rice University. I wish I had met him earlier, because I was hooked from then on, and knew that I wanted to enter the field. Although I had been somewhat familiar with nanotechnology and MEMS since high school, I had never heard anything about microfluidics. I can only imagine what would have happened if I had started learning about the field when I was in high school. With the increasing presence of the microfluidics, it only makes sense to have people learn about it before they're working on it for their Master's or PhD, or seeing it in the news. That's the goal of Dr. Michelle Khine et al. of University of California Irvine. In case you're not familiar with Dr. Khine, you may remember her as one of the 2009 TR35 recipients. It's an award by MIT's Technology Review that recognizes young innovators under 35.In the paper "Shrink-film microfluidic education modules: Complete devices within minutes," which was published in Biomicrofluidics in June 2011, they outline a plan to introduce the field to middle schools, high schools and undergraduate programs. When compared to standard techniques, microfluidic systems can boast faster reaction times, portability and lower sample usage. Despite these advantages, they are still traditionally expensive to produce, which has limited their accessibility outside high-tech companies and universities. The authors of the paper note that thermoplastics (among other materials) are a low cost alternative fabrication technique that can also be used for education.Thermoplastics are essentially Shrinky Dinks you might have played with as a kid. You can draw on them, and they'll shrink when heated. The authors developed experiments using this material for middle school, high school and college classes, in which each level draws from and expands on the one before it. Using computer-aided design (CAD), the students are able to design their devices, and print them onto the plastic using a printer. After heating the plastic to shrink it to 95% its original size, it's used as a mold to create the device.H filterThe basic module for the middle school students is comprised of an H-filter. An H-filter is a simple microfluidic structure that is able to sort particles by their size without a membrane. The students replicate the filtration of blood using different sized microbeads. The results of the filtration can readily be seen.In addition to the previous module, high school students can build a microfluidic device that creates a gradient. A lot of biological processes are driven by gradients, making it a key environment to reproduce. The gradient generator design features branching and mixing channels that take inputs of plain water and dyed water to produce a gradient of concentrations at the end. Gradient GeneratorIn order to add a level of complexity for the gradient generator in a college classroom, it has been combined with an immunoassay. The channels of the structure are first coated with a primary antibody. A secondary fluorescent antibody is then fed through one inlet, as a serum is fed through the other. The resulting fluorescence indicates the same gradient occurs as was seen with the food dye previously.I think that this paper not only illustrates something cool to teach students, but takes it two steps further. It first illustrates some of the interesting characteristics of microfluidics such as diffusion mixing and laminar flow. It then illustrates possible applications of the technology in diagnostics or point-of-care devices. As microfluidics education grows, I think we'll eventually see grad students who started learning the same year as their mentors!Reference:Nguyen, D., McLane, J., Lew, V., Pegan, J., & Khine, M. (2011). Shrink-film microfluidic education modules: Complete devices within minutes Biomicrofluidics, 5 (2) DOI: 10.1063/1.3576930Claim token: blog4e48131515be7... Read more »
Nguyen, D., McLane, J., Lew, V., Pegan, J., & Khine, M. (2011) Shrink-film microfluidic education modules: Complete devices within minutes. Biomicrofluidics, 5(2), 22209. DOI: 10.1063/1.3576930
In case you didn’t get the first part of my title, let me tell you a little about centrifugation. Centrifugation is a very common research technique. A solution is centrifuged to isolate suspended particles by spinning it around at high speeds. Depending on the weight of the particles and the force of the centrifuge, the heavier particles will form a pellet at the bottom of the container. The rest will still be suspended in fluid. Depending on which particles you’re after, you can continue doing this by removing the fluid and changing the forces in order to manipulate which particles form the next pellet. But in between each step the pellet must be resuspended and is vortexed (with a vortex mixer) to break up the pellet. Now, keep the definition of vortexing and the process of centrifugation in mind.Researchers from the University of California, Los Angeles have proposed a ‘Centrifuge-on-a-Chip’ that would replace its bench top counterpart. The article, “Automated cellular sample preparation using a Centrifuge-on-a-Chip” by Di Carlo et al. was featured on the cover of the 2011 Issue 17 of Lab on a Chip. The article proposes a streamlined system that requires no external forces which, like I said before, makes it much more powerful. In order to evaluate the competency of new technology we need to compare it to a golden standard that accomplishes its task the best, no matter how long it may take. In this case, it is the centrifuge and we’ll monitor its three main jobs throughout this post:Separation of cells by size or density
Concentration of cells
Labeling of cells via solution exchange
The authors’ forceless Centrifuge-on-a-Chip is defined by its structure. It features a simple channel that suddenly widens. It is this widening that creates vortexes, enabling filtration. When the particles were flowing through the plain channel, they were held in place by a force that pushes them towards the wall and a force by the wall that pushes them away. When the channel widens (the wall effectively disappears) they succumb to the force pushing them away from the center of the channel. The rate that particles move out of the channel area, into the vortex region, is proportional to their size (greater than the square of the diameter). Therefore only particles above a certain threshold can be captured. The particles are able to be selectively released from their orbits by decreasing the flow rate.Beyond simply organizing different beads, the authors validate the filtration process by separating and concentrating circulating tumor cells (CTCs) from dilute blood. Given that CTCs can be 33% to 900% greater than size than blood cells, they should be able to be separated using the vortices. This was confirmed by processing 10 ml samples with ~500 CTCs and 2.5 billion blood cells. The end result was a volume of 200 µl that recovered about 20% of the CTCs, which constituted 40% of the volume.Now, so far we’ve been able to see the device filter cells by size and concentrate the cells, both things on our list. The only thing left to do is see if this is able to label the cells like a normal centrifugation process can. In order to traditionally label cells, they must first be incubated with the labels and centrifuged into a pellet. The fluid with extra labels must be removed and then the cells are resuspended. With the Centrifuge-On-A-Chip, the cells merely have to be caught in a vortex, exposed to the labels and rinsed. The traditional and new techniques were used to label intracellular proteins, cell surface proteins, enzyme substrates and DNA. I’m not a labeling expert, but the comparison between the two techniques seems pretty similar. There seems to be more of a difference for the labeling of the cell surface proteins, but I’m not sure if it is significant. They also demonstrated the ability to tag with primary and secondary antibodies, as well as microbeads. After 5 minutes the vortexed cells were labeled with the same number of microbeads as the traditional cells after 30 min (the same amount of labels was used for both techniques in all experiments). Further, after 30 minutes, the vortexed cells had twice the number of microbeads as the traditional cells. Safe to say, this technique can definitely label cells at least as well as the traditional method.The Centrifuge-On-A-Chip is clearly a viable contender against the traditional bench top centrifuge and its techniques. While there is no given price for each device, or how many devices would be necessary to provide the same output as a centrifuge, it will certainly cost less than thousands of dollars. Additionally, it is portable and can process the tasks in less time. When compared to the Centrifuge-On-A-Chip’s competitors, it still comes off fairly well. Some others are only able to filter cells and not concentrate them. Some immobilize the cells on membranes, which may prevent them from performing assays, or may clog the membranes. There was also no change in viability before and after the vortexing. However, it is necessary to dilute the blood before it can be processed, but I doubt that this would be negative enough to prevent someone from using this entirely. I suppose that we’ll just have to wait and see how quickly this can enter the market, and how cheaply it can be produced.Reference:Mach, A., Kim, J., Arshi, A., Hur, S., & Di Carlo, D. (2011). Automated cellular sample preparation using a Centrifuge-on-a-Chip Lab on a Chip, 11 (17), 2827-2834 DOI: 10.1039/c1lc20330d... Read more »
Mach, A., Kim, J., Arshi, A., Hur, S., & Di Carlo, D. (2011) Automated cellular sample preparation using a Centrifuge-on-a-Chip. Lab on a Chip, 11(17), 2827-2834. DOI: 10.1039/c1lc20330d
Seeing really is believing. How often can we tell what a liquid is by just looking at it? Not too often. Sure, you might be able to tell when you definitely smell something sulfurous, or have a slippery base and I hope you can pick out milk. But we’re not always that lucky, especially if you’re dealing with something you really shouldn’t be touching or directly smelling. There are a ton of tests we can run to pinpoint what it is and you often need a pro to decipher the results. Ideally you could just read it with your eyes. With a batch of research from Harvard University, we’re one step closer. The paper entitled, “Encoding Complex Wettability Patterns in Chemically Functionalized 3D Photonic Crystals” was featured in the August issue of the Journal of the American Chemical Society. The lead authors Ian B. Burgess and Joanna Aizenberg, of the Wyss Institute, propose a process to functionalize crystals so that they can differentiate between different fluids. First, these aren’t just any of crystals. These are 3D porous photonic Inverse Opal Films (IOF). They were carefully created to maintain a specific structure. The ability to discern between different fluids is possible due to selective application and erasure of different chemicals. First, a functional group is applied to the surface of the IOF. A slab of PDMS (a silicon-based polymer) is sealed to an area of the IOF. O2 plasma is applied and erases the functional group except the area covered by the PDMS. This can then be repated with a second functional group, and so on and so on. There can even be overlapping areas covered to give you exactly what you need. But what’s the point of functionalizing the surface? Well the functionalization affects the wettability of the IOF. Given the surface’s wettability and the surface tension of a liquid, the liquid won’t be able to penetrate the channels. There can be a clear change of color in the infiltrated regions. The authors refer to their system as Watermark-Ink (W-Ink) and suggest that it could be used as security measures. But I think I’d rather see it used in microfluidics. While you may toy with the notion that you could selectively choose which fluids flow through certain channels and partake in reactions, I think it is most useful as an indicator. Many microfluidic devices are intended to be used as point-of-care (POC) diagnostics. A sample is analyzed for a certain component that would indicate something about the patient's health. But at the end of the test, you have to be able to tell if the reactions were positive or negative. I think that the test could be designed to produce two fluids with different surface tensions, depending on the outcome. Then, one of two shapes would appear. It would require no confocal microscope or camera, and certainly wouldn’t need translation.Reference:Burgess, I., Mishchenko, L., Hatton, B., Kolle, M., Lončar, M., & Aizenberg, J. (2011). Encoding Complex Wettability Patterns in Chemically Functionalized 3D Photonic Crystals Journal of the American Chemical Society, 133 (32), 12430-12432 DOI: 10.1021/ja2053013... Read more »
Burgess, I., Mishchenko, L., Hatton, B., Kolle, M., Lončar, M., & Aizenberg, J. (2011) Encoding Complex Wettability Patterns in Chemically Functionalized 3D Photonic Crystals. Journal of the American Chemical Society, 133(32), 12430-12432. DOI: 10.1021/ja2053013
Digital Microfluidics BackgroundWith the widespread use of electronics, we often use the word ‘digital,’ but we might not always think about what it actually means. For those of you who have never taken a class in electrical engineering, or never learned Latin (from the word digitus), the word describes anything that is discrete as opposed to continuous. Digital has also been applied to a type of microfluidics. With the definition in hand, you might guess that digital microfluidics does not describe continuous fluid flow through channels at the micro- scale, but instead is made of droplets. Discrete droplets can be implemented in a variety of assays or devices, as they would allow for complete control of the fluid, instead of a continuous stream of fluid that may not be thoroughly mixed. Regardless of the intended use of the droplets, they must first be created.There are currently three techniques to generate droplets:electrowetting
Electrowetting essentially uses an electric field to change how fluid interacts with the surface. It can make the surface more or less attracted to water, causing a fluid such as water to 'hug' the substrate or 'ball up' into a droplet. Manipulation of the electric field would provide control of the locations of droplets and how they move. Check out the videos from Dr. Richard Fair's laboratory at Duke that illustrate the formation and transportation of droplets using electrowetting.Dielectrophoresis occurs when nonuniform electric fields cause polarizable particles to move. The application of dielectrophoresis for microfluidics was proposed by Dr. Thomas B Jones in the Journal of Applied Physics in 2001. Water is attracted to the regions where the electric field is the strongest. This movie from Jones does not demonstrate the formation of droplet formation, but it does illustrate its control over water.Finally, the process of emulsification describes a system of two fluids in which one fluid is dispersed throughout the other. Think water and oil and the droplets you can create when you shake it around. This first requires at least two fluids to be used (I say at least two, because multiple emulsions can be achieved, as seen here) and an external stimulus. An external stimulus is often needed to cause stable droplet formation. This can occur at junctions, where specific geometry, along with control of flow rates can cause emulsification. You can see a video at the company RainDance's website. They have more information on the subject, and I recommend that you check out their other videos on that page, especially 'Loading droplets.' It's like a gumball machine!UV Controlled Droplet FormationWhile the ability to digitize fluid is valuable, its regulation can be increasingly more prized. Does the digitization have an on/off switch? Do you have to change the flow rates of the system to revert back to continuous flow, or physically move components that are responsible for pinching the droplets? The capability to switch between continuous and digital flow could serve to reduce the footprint of the device. Why make the system larger just to incorporate streams and droplets when it can happen in the same place? This would lend elegance to the design of the device. The sophistication would be improved if this could be accomplished without moving parts. The most reliable instruments and devices have fewer moving parts that could break down. This might be what Damien Baigl et al. from École Normale Supérieure in France had in mind. Their research, which was featured on the cover of the 2011 Issue 16 of Lab on a Chip, proposes a method to emulsify droplets with Ultraviolet (UV) light. Their paper entitled, "Photoreversible fragmentation of a liquid interface for micro-droplet generation by light actuation" describes an emulsification system that is controlled by the use of UV light.Droplets form at junction with UV lightTo start, the system has water-in-oil flow. But the water contains a surfactant AzoTAB. When UV light is applied to this compound, a double covalent bond switches (from trans to cis). This causes the surfactant to become more polar and decrease the wettability with the surface of the device. The lowered wettability causes the water with AzoTAB to form droplets. Initially the researchers created a junction that was capable of emulsification depending on the flow rates of the fluid. They were also able to find a combination of flow rates that would not normally create droplets, but digitized with UV light.Droplets form in open channel with UV lightWhile this is a nice feature, it partially relies on the preexisting stru... Read more »
Diguet, A., Li, H., Queyriaux, N., Chen, Y., & Baigl, D. (2011) Photoreversible fragmentation of a liquid interface for micro-droplet generation by light actuation. Lab on a Chip, 11(16), 2666-2669. DOI: 10.1039/C1LC20328B
I'm slowly working my way through Olaf Sporn's excellent book, Networks of the Mind. The purpose of this book is to introduce neuroscientists to network theory, and vice versa; I'm eavesdropping and tooling up on both. It's slow going only because it's pretty much all new territory to me, but I'm seeing a lot of potential in the overall approach to the brain, and this just confirms for me that Sporns understands what he does pretty deeply.
Anyway, a while back, Bruce Hood tweeted the following:
Fact: in the digestive tract of the lobster, its nervous system can have
100k-200k different neural states that produce the same behavior
This struck me as an astonishing fact; to my mind, it throws the idea that hunting for the neural correlates of behaviour into serious doubt. At the very least, it needs to radically change what you expect to find. I finally found the reference for this fact in Sporns' book (Prinz, Bucher & Marder, 2004; download), and Sporns has some interesting context for this fact (which Hood undersells - see below) and why it's interesting, rather than soul-crushingly depressing. There are some interesting potential consequences relevant to my current ponderings on the brain, although it's definitely still at the 'these sound like the same sort of principle' level of analysis.
Inter-individual variation is a fact of cortical organisation; while a given type of brain (e.g. human) exhibits broad structural similarity the specific details are enormously variable. However, these structurally variable brains support functionally similar behaviour - this is referred to as degeneracy:
Structurally variable but functionally equivalent networks are an example of degeneracy, defined as the capacity of systems to perform similar functions despite differences in the way they are configured and connected (Tononi et al, 1999; Edelman & Gally, 2001)
Sporns, 2010, pg. 69
Degeneracy is a strength, not a weakness of a system. It provides critical redundancy to a system, so that it can continue to exhibit a given behaviour in the face of noise or damage (an ability which Sporns also refers to as functional homeostasis). It's also a ubiquitous feature of biological systems across multiple scales, presumably because these continually face the task of performing the same basic function under highly variable conditions.
Degeneracy in the humble lobster gut
The Prinz et al (2004) paper is an astonishing demonstration of the degree of degeneracy available to even a simple neural system. They begin by noting that neuroscience typically treats variation as noise, and removes it by averaging, etc. They were wondering how justifiable this is. To understand the functional consequences of structural variation, they modelled a simple motor circuit in the lobster (technically, the pyloric rhythm of the crustacean stomatogastric ganglion). Combining all legitimate neuron types and synapse strengths gave them 20,500,000 model circuits. They then simulated the motor output of all of these circuits. 4,047,375 (20%) of these produce a pyloric-like output; this was reduced to 452,516 when the simulation was constrained by recordings from lobsters, and even here all 150 possible combinations of neurons were capable of producing pyloric-like activity. Finally, pyloric-like activity occurred for synapse weights across the entire functional range (with the exception of one particular synapse weight which had to be very weak: this, it turns out, matches the biology of the actual system very nicely). In effect, the behaviour of the network (and not just the individual neurons) exhibited extraordinary functional homeostasis (450,000 ways to produce the same rhythm) and the parameters were stable over several orders of magnitude (so long as the appropriate compensation has occurred elsewhere in the network).
The lesson: the nervous system is not trying to maintain a specific set of wiring connections and weights; it is trying to maintain the capacity to perform a specific function. Prinz et al's analysis supports the idea that this function can be defined at the network level, not just at the level of individual neurons (and I'm going to suggest this principle extends to perception-actions systems as well). Sporns then notes that this is clearly a feature, not a bug:
Such homeostatic mechanisms are essential for the long-term stability of the brain given the continual remodeling and structural turnover of its cellular and molecular components
Sporns, 2010, pg.68
This reminds me of something I saw in Sporns cognitive neuroscience class at IU; video of neurons extruding and retracting axons, forming and reforming connections,something they apparently simply never stop doing. I've never forgotten just how busy the neuron was, on a millisecond time scale; structural stability is clearly not what the brain is interested in. There is, therefore, tremendous and ongoing flux that is part of the normal operation of the brain (let alone what happens following injury) and this degeneracy provides this dynamic system with functional stability in the face of these perturbations.
Some implications for the brain
This implies a couple of things. First, the brain is not static in any way, not even the ways we first thought might be necessary to preserve stable function. The brain is in the state it's in through use, and that use can produce all kinds of variability that don't affect function.
Second, this variability will be both within and between people; Sporns again:
Price and Friston have noted that human brain networks display degeneracy since different sets of brain regions can support a given cognitive function (Price and Friston, 2002). Cortical activation maps obtained from functional neuroimaging studies of individuals often show only partial overlap for a given cognitive task, suggesting that different individuals utilize different (degenerate) networks.
Sporns, 2010, pg. 69
While this doesn't make neuroimaging useless, it is an important caveat that is rarely remembered. This kind of variability is also the reason that there are limited lessons to be learned from clinical cases; while these are interesting and do provide hints as to what regions of the brain are involved in, but
The loss of a subset of all regions that are reliably activated in a given task may not disrupt task performance, indicating that individual regions may not be necessary or that recovery processes following brain injury can configure structurally different but functionally equivalent networks.
Sporns, 2010, pg. 69
It's not clear to me that much of cognitive neuroscience is worrying about this, although clearly people like Sporns are.
Degeneracy in perception-action systems
This organising principle (preserve functional outcome, implement it with whatever you've got) actually extends to the level of the perception-action system. Take a task like reach-to-grasp (prehension); you can implement the functional outcome of transporting your hand from where it is to the object via an indefinitely large set of movements. We typically produce very efficient, very stereotyped prehension movements to a given target, but that's only true when the system's resources remain the same. If you change any part of this task (the distance to the object, the size of the object, the goal of the prehension movement) the prehension movement will rescale itself to match and thus preserve the outcome. My colleague Mark Mon-Williams talks a lot about end-point control - prehension is organised with respect to the control of the hand, not the intermediate joint configurations, and those simply do what's required.
A recent article demonstrated this type of principle. Castro et al (2011) investigated what the system is learning when it corrects errors. There are two options: adapt your next movement as a function of the error with respect to what you planned to do, or as a fu... Read more »
Gonzalez Castro LN, Monsen CB, & Smith MA. (2011) The binding of learning to action in motor adaptation. PLoS computational biology, 7(6). PMID: 21731476
Prinz, A., Bucher, D., & Marder, E. (2004) Similar network activity from disparate circuit parameters. Nature Neuroscience, 7(12), 1345-1352. DOI: 10.1038/nn1352
Brief overview of the role of chemotaxis in yeast mating, plus new research on highly efficient and dynamic cell-to-cell signaling during yeast mating.... Read more »
Meng Jin,1 Beverly Errede,1* Marcelo Behar,2 Will Mather,3 Sujata Nayak,3 Jeff Hasty,3, & Henrik G. Dohlman,1,4 Timothy C. Elston4*. (2011) Yeast Dynamically Modify Their Environment to Achieve Better Mating Efficiency. Science Signaling , 4(186). info:/
There is a very interesting new paper that just came online in the Archives of Pathology: Rapidly Progressive, Fatal, Inhalation Anthrax-Like Infection in a Human: Case Report, Pathogen Genome Sequencing, Pathology, and Coordinated Response
I was alerted to the paper by Eileen Choffnes of the National Academy of Sciences Institute of Medicine Forum on Microbial Threats (which I am a member of). In the paper, James Musser, Angela Wright and colleagues, the authors discuss the use of genome sequencing in the characterization of a fatal infection with a bacterium that appeared to be a species of Bacillus. Their summary is below and pretty much sums it up:
...... READ MORE .......
This is from the "Tree of Life Blog"
of Jonathan Eisen, an evolutionary biologist and Open Access advocate
at the University of California, Davis. For short updates, follow me on Twitter.
... Read more »
Wright AM, Beres SB, Consamus EN, Long SW, Flores AR, Barrios R, Richter GS, Oh SY, Garufi G, Maier H.... (2011) Rapidly Progressive, Fatal, Inhalation Anthraxlike Infection in a Human: Case Report, Pathogen Genome Sequencing, Pathology, and Coordinated Response. Archives of pathology . PMID: 21827220
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